Method and system for analysis of biological signals such as dynamic electrocardiograms and the like

ABSTRACT

Method of analyzing biological signals, including obtaining a magnetic recording media having an analog biological signal recorded thereon, using digital processing software to digitize the biological signal, displaying the digitized biological signal in analog form on a display, and visually analyzing the biological signal on the display. The biological signal may be an electrocardiogram. Preferably, independent channel enhancement of the dynamic range of the analog biological signal is performed prior to digitizing The displayed biological signal is preferably presented in time compressed form. Digitizing is performed by sampling the biological signal at at least approximately 44,100 Hz per second per channel and quantization of at least 16-bits per sample per channel. The digital processing software is preferably digital audio processing software.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application hereby claims priority on U.S. ProvisionalApplication No. 60/103,154 filed Oct. 5, 1998, the disclosure of whichis hereby incorporated by reference herein in its entirety.

FIELD OF THE INVENTION

[0002] The instant invention relates to improved methods and systems foranalysis of dynamic electrocardiograms and other similar waves ofbiological origin with the purpose of facilitating improved diagnosis ofpathological states in human and veterinary medicine. More particularly,the instant invention advantageously uses advances in sound wavetechnology to improve the recovery, preservation, enhancement and costeffective analysis of biological signals to aid research as well asmedical and veterinary diagnosis.

BACKGROUND OF THE INVENTION

[0003] Coronary heart disease is the main cause of death in manycountries. About 50% of those affected do not reach the hospital due topoor recognition of the disease before a cataclysmic, often terminalevent has occurred. The present invention facilitates improvedrecognition of myocardial ischemia in and out of the hospital by laypeople with minimum training. Once the nature of the event isrecognized, prompt treatment can then be obtained with a net effect inthe decrease of morbidity and mortality and thereby providingsubstantial gains in life span and in quality of life.

[0004] Heretofore, visual analysis of the ambulatory electrocardiogram,in its original analog format, has been and remains unsurpassed and itis superior to any and all current computerized forms of analysis.Visual analysis is a very time consuming (hence costly) process, whichrequired an operator with intimate knowledge of electrocardiography andcardiology. For this reason the use of visual analysis has been limitedto academic research and it has not been possible to extend its benefitto patient care in the community. The instant invention overcomes thisproblem and enables identification of the abnormal patterns by anyperson with normal intelligence with a minimum (few hours) amount oftraining in the recognition of the discrete visual patterns which arerepetitive between and within patients.

[0005] The instant invention, referred to herein as the ComputerizedVisual Analysis Technique or “CVAT”, generally relates to the use ofstate-of-the-art electronics, computer hardware and software and forwardlooking signal analysis principles of technology for the evaluation ofbiological signals obtained from isolated cells, tissues, human andanimal species to aid research and diagnosis of medical and veterinarydisease states. CVAT can be used to process biologic signals such as,but not limited to: 1) the electrocardiogram in all it's forms, and inparticular, the continues electrocardiographic signal such as thatobtained with the Holter technique or during on-line, real timemonitoring of a patient; 2) the electroencephalogram; 3) the myogram; 4)the phonocardiogram; and 5) Respiratory sound waves including theircorrelation with the electrocardiogram and encephalogram to diagnosesleep disorders in the hospital and in out of hospital settings.

[0006] CVAT remedies major limitations of the current Holter analysisparadigm which is useful only to detect gross arrhythmia on the 24-hrelectrocardiogram (ECG). Current computerized analysis of the ambulatoryECG is done without due regards for protection of the integrity,fidelity, resolution or dynamic range of the analog signal recorded. Thecurrent methods are unable to reliably detect ambulatory ischemia orrisk for potentially lethal arrhythmia. Such risks are not detectable ina cost-effective manner with prior art techniques. These shortcomings ofthe prior art have a significant impact on cardiovascular morbidity andmortality. CVAT remedies the failure of the current methodology bymaking full use of the valuable information encoded in the ambulatoryelectrocardiogram. By failing to disclose evidence of risks forcatastrophic events, current Holter analysis lulls clinicians into thefalsehood of absence of evidence misrepresented as evidence of absenceof potentially lethal risks. Consecutive obsolete methodologic steps incurrent Holter analysis severely diminish the quantity and degrade thequality of the signal encoded in original Holter recording media.

[0007] Mass screening for patients silently at risk for potentiallylethal cardiovascular events could save hundreds of thousands lives inthe United States alone. Well done ambulatory ECG monitoring is the onlymethod able to detect transient myocardial ischemia and spontaneouslyoccurring electrical alternans. More than half of the myocardialinfarcts and sudden cardiac deaths happen without any prior history ofcardiac disease. The instant inventor has determined that these occultand lethal risks can be detected and lives saved if Holter analysis isdone with all the resources made available by the fast advancesconstantly made in signal analysis and computer technology.

[0008] As many as 80 to 100% of the myocardial ischemic episodes in apatient can be asymptomatic or have uncharacteristic manifestationsknown as “anginal equivalents” by cardiologists but frequentlyundetected by non-cardiologists. Silent and or uncharacteristic ischemicevents are common especially in females, diabetics, hypertensives,smokers, hypercholesterolemics, etc. Endothelial cell dysfunction andoccult coronary heart disease are frequently hidden pathophysiologiccauses of catastrophic or lethal cardiac events.

[0009] Silent ischemia, especially that which is not induced by physicalstress, can be detected only by ambulatory ECG. However, today, the onlyreliable form of Holter analysis is visual scanning of the magnetic tapeitself, not the “over reading” of the expunged and distorted digitalfile which misrepresents the original signal. Visual analysis by anexpert electrocardiographer is a very time consuming method used only byhighly motivated experts in research programs. Due to time and costinvolved, visual analysis of the analog signal cannot be applied toclinical practice or mass screening of at risk population with knownmethods. To detect ischemia, special attention must be paid to microvoltrange changes in the ECG, which are not preserved or duly analyzed bycurrent Holter algorithms. There is a need in the art to develop animproved method of Holter analysis that can be made cost effective bynot requiring highly sophisticated operator skills. In accordance withthe invention, preservation of the signal integrity, dynamic range,fidelity and resolution in the time and voltage domains are of paramountimportance for accurate diagnosis of electrocardiographic abnormalities.These considerations are literally of vital importance especiallyregarding the microvolt region of the ECG where the ventricularrepolarization is encoded.

[0010] The current computerized methods of Holter analysis usecommunications engineering techniques and thoroughly obsolete computerhardware and software. Communications engineering paradigms andtechniques are best limited to the evaluation of non-biological signalswhere reproducibility and repetition of waves and other phenomena arethe norm. Biologic signals, such as the electrocardiogram, arise fromcomplex biological entities where individuality, constant variation andirreproducibility are expected. A major drawback of engineeringautocorrelation is that it is sensitive to waveform changes in the timedomain (X-axes) and poorly sensitive to changes in the voltage domain(Y-axes). In current Holter analysis, autocorrelation is wrongly appliedto a small sample of degraded biological signal with poor dynamic gainwhich magnifies the limitations of autocorrelation to recognize voltagechanges. Non-biological techniques used to analyze biological datayield, at best, mediocre results, which become poor when analysis isdone using a distorted, minuscule fraction of the original signalrecorded.

[0011] The present invention remedies the deficiency of the current artby completely turning away from over reliance in engineering paradigmsnot applicable to biology and technology and methodology which has longbecome obsolete. Rather than using autocorrelational techniques, CVATanalyzes morphology, visual patterns and internal harmony in the timeintervals. Since it's discovery at the beginning of the century,electrocardiography remains a highly visual, pattern and morphologybased discipline. Despite sophisticated efforts (such as neural networkor fractal strategies) to advance computer science, humans still dobetter visual pattern recognition than computers. In CVAT, morphologicpatterns are quickly and easily recognized by non sophisticatedtechnicians. Expansion of abnormal, visually compressed, ECG patternslead to precise identification of important, classicalelectrocardiographic signs that can not be identified by current Holteranalysis. CVAT evaluates time intervals as reflection of harmony ordisharmony within the recording; comparisons with the “norm” are donewith caution. Current Holter computer analysis relies on quantificationof duration and voltages in a digital file degraded in quantity andquality to compare these findings to idealized “normal” values obtainedwith different and better equipment.

[0012] There are two basic types of ambulatory ECG recording systems.The “retrospective” system (commonly known as Holter recording) analyzesthe collected data after completion of the signal recording phase. The“real-time” system analyzes data as it is being recorded. Retrospectivesystems record the ECG on magnetic tape (usually the cassette type) orflash cards to subsequently analyze the data. In either system, therecording is done through a plurality of input leads attached throughelectrodes to various points on the patient's chest. To analyze the ECG,real-time systems generally include a microprocessor in conjunction withthe electronic storage device. Both the real-time and the retrospectiverecording systems are designed to interface with a scanner through amagnetic tape reader or an electronic interface to download thecollected information for analysis, editing, storage, and reporting.

[0013] To record sound, cassette decks use a magnetic tape speed of 55mm per second across the recording head. For Holter recording the tapespeed is reduced 50 to 100 times to speeds of 1.1 to 0.55 mm per second.Such drastic speed reduction is necessary to do 24 hours recordingswithout changing cassettes. Speed fluctuation in the 10% range is asignal acquisition problem; the best research efforts have dropped it to3%, which is still too high for accurate quantitative ECG analysis. Thetime-base fluctuation is magnified when the low-speed recording isplayed back at very high speeds. The magnetic tape is orders ofmagnitude richer in signal quantity and quality than the very smalldigital file used for current forms of analysis. The norm today is todigitize the analog signal by playing back the cassette tapes at speedsas fast as 480 times real time; this is the beginning of majordegradation of the analog ECG.

[0014] Cassette tape decks used for Holter processing are inexpensive,less than precise instruments. High-speed playback degrades fidelity bylimiting frequency response. Inaccuracy and signal deterioration is alsointroduced by biasing and/or misalignment of the tape on the play backhead during highspeed play back. Tape stretching due to repeatedstopping and starting of the tape is another source of signaldegradation. CVAT solves these problems, in part, by using the highquality decks to play back the tape once, in an uninterrupted manner, ata speed preferably lower than 37 times real time. The digital signalmay, for example, then be copied from a hard drive and archived in acompact disc.

[0015] Independent channel enhancement of the dynamic range is animportant step introduced by CVAT and not done in the current Holterart. The signal encoded in each channel of the magnetic tape is fed intoa sound mixer for independent expansion of the dynamic range prior todigital encoding using the best possible or high quality sound card. Inaccordance with the invention, sampling of the analog signal ispreferably done at rates of 44,100 to 96,000 Hz with 16-bitsquantization, per sample, per channel. Higher sampling and quantizationrates may also be used. The current Holter art samples, at best, at8,000 Hz with 8-bits cards without preservation of the signal integrityor enhancement of dynamic range prior to analog to digital conversion.

[0016] Current Holter analysis is entirely dependent upon the extractionof an unselected fraction of the analog signal encoded in a 24-hourHolter tape. Current algorithms use elision and omission of vast amountsof the originally recorded ECG signal to achieve extreme, unnecessaryand deleterious data compression. For instance, at the June 1999 DrugInformation Association meeting, Mortara et al. announced, as a novelachievement, the launch of 24 hr 12 leads Holter that will be stored in16 megabytes of a flash card (over 100,000 heart beats in 1.33 MB perlead per 24 hr). Obsolete clipping and distortion of the signal housedin novel media.

[0017] On the surface, the quest for radical compression strategies(“decimating”) would seem to be adequate in that it saves memory andgreatly enhances the portability of Holter data. However, extremedigital compression gravely decreases the integrity, fidelity,resolution and most importantly the dynamic range of the storedelectrocardiogram or any other signal. Furthermore, in the current art,Fast Fourier Transformation is used to artfully create “imaginarypoints” to replace discarded original data and “smooth” the nowpartially fictitious signal. Such creative approach is done afterdrastic lossy compression has irretrievably discarded more than 90% ofthe original signal with great loss of integrity, dynamic range,resolution and fidelity. The end product is the current art's inabilityto detect ischemia, pacemaker-malfunction, arrythmogenic risk or anycondition other than gross ventricular arrhythmia.

[0018] Gross data clipping and “imaginary” data points only partiallyexplain the major limitations of today's Holter analysis. The continuinguse of vastly outmoded computer and signal processing technology impedethe use of Dr. Norman Holter's invention to it's full diagnosticpotential to save human lives. Data compression strategies used incurrent Holter analysis date back to the accidental creation of the Y2Kproblem. Obsolete and unnecessary compression strategies reduce 24-hoursworth of analog Holter data down to a little more than a single megabytedigital file. When the algorithms for Holter analysis were created,extreme limitations in available memory existed. Thus, extreme datacompression was needed. It is not accidental that the 1 megabyte andfraction file was perfectly portable in a single 3.5″ magnetic floppydisk and suitable for telephonic transmission with now grossly obsoletemodems. The fact that Apple Computers, Inc. has altogether ceased toissue computers with 3.5″ magnetic floppy disk drives is an indicationof how outmoded such a standard for data-volume has become. Thirty yearsago, in the infancy of the computer industry, when silicon chips were asexpensive as they were limited in their RAM or ROM capacity, datacompression was a necessary evil. The Y2K problem was created by ageneration of computer programmers who, squeezing every last bit ofpossibly available data space from the mainframes and PCs of the past,deemed it frivolous to reserve then-precious RAM or ROM memory for thetwo digits ‘19’ in any and all indications of the year. Now thatcomputer memory is as cheap as it is truly vast in capacity, datacompression is an undesirable tool mainly used by producers ofentertainment and other non-essential computer applications, i.e.whenever loss of data is deemed acceptable for reasons of practicalityand/or fast transmission over consumer-level internet connections.

[0019] Like all biologic signals, ECG, as audio data are remarkably hardto compress effectively. All compression routines are known todeteriorate dynamic range, signal quantity and quality. For 8-bit data,a Huffman encoding of the deltas between points has been used in currentHolter analysis but deterioration of the signal is quite evident. For16-bit data, companies like Sony and Philips are spending millions ofdollars to develop proprietary schemes that as yet are not fullysuccessful. If somehow, truly non-lossy audio compression would becomeable to compress 350 megabytes (the size of a CVAT 24 hr ECG file) ofdata and, even more importantly, preserve high fidelity, resolution anddynamic range intact within a single megabyte of memory, such acompression strategy would be almost a miraculous gift to the computerindustry and technology in general. Although great strides of innovationare now being made in techniques of data compression, a 350:1 datacompression ratio keeping the integrity of the signal is as yetimpossible, nor is it necessary. The fundamental pitfalls of currentHolter algorithms are the same than those which were silently at work inthe creation of the Y2K bug: automated data compression algorithms whichdiscard data deemed inessential to the projected application. To be ofany value, pre-compression selection of data to be invisible, inaudible,illegible, or otherwise useless, is a must. The problem is that suchpre-compression decision regarding ambulatory ECG signal is not and cannot be made without rendering compressed Holter files useless except fordetection of gross arrhythmia.

[0020] The much-hyped MPEG Layer 3 (or ‘MP3’) strategy of digital audiocompression, for instance, uses a psychoacoustic algorithm to determinewhich sonic frequencies in a given audio recording remain ultimatelyaudible to the ear of a listener. The data corresponding to all‘irrelevant’ frequencies are then omitted from the resulting compressedsound files. Although the algorithm used in MP3 compression is quiteadvanced, the process still degrades the quality of the original signalin an invariably noticeable (almost ‘trademark’) fashion. Suchdegradation, however, lies within an ‘acceptable’ window of loss for theconsumer-oriented purposes of the technology, i.e. exchanging recordingsof popular songs over the Internet. Boasting a powerful 12:1 compressionratio, MP3 is a fairly new compression strategy. Even newer, ‘better’strategies are being invented on almost a quarterly basis, but all ofthem, even the latest ‘fractal’ compression strategies, still ultimatelyboil down to the same compression paradigm: automation of the a prioridecision to selectively preserve or omit certain types of data.Detection of microvolt and lower voltage changes in the ECG isrelatively new in the electrophysiology lab and now brought toambulatory ECG with the instant CVAT method. It is not yet known whichvoltage changes are unimportant and to be disposed with impunity.

[0021] One overriding fact remains clear: the application of anyinherently omissive data compression strategies to a 24 hr ECG recordingprior to any and all analysis of the totality of the signal is wrong.The only possible use of such indiscriminately selected file isdetection of conditions expected to be apparent within the grosslycompressed version of the ECG signal. For the current Holter analysis,that condition was and remains gross arrhythmic events. For a phenomenonas eponymously elusive as ‘silent ischemia’, for instance, such a starkpredetermination of what will and will not be detectable in anelectrocardiogram is, literally, the most fatal omission of all.Detection of silent ischemia and risk of fatal arrhythmia is done in themicrovolt region of the signal, the area that suffers the most fromdynamic range and signal quality deterioration due to obsolete signalprocessing schemes. Current Holter analysis continuing reliance uponobsolete signal and data handling strategies limits access only to thatportion of ECG data which was thought worth representing within a singlemegabyte of computer memory more than 10 years ago. Holter analysisremains a vastly under addressed technological obsolescence which is anobstacle for detection of risk for lethal events and in doing so putslives directly at risk.

[0022] The numbers speak for themselves: Digital compression of 24 hoursof recorded signal down to as low as a single megabyte unnecessarilyomits about 99.6% of the ECG which can be easily retrieved from theaverage 24-hour magnetic Holter tape. It is like attempting to “read” abook while missing 99.6% of the words or “watch” a film with 99.6% ofthe celluloid frames omitted. Diagnosis of potentially life threateningconditions can and should not be made based on such scanty andnon-discriminatingly selected fraction of the ECG stored in the originalrecording media. Human life protection deserves better than that.

[0023] The instant CVAT process for Holter analysis utilizes acompletely different method of “data compression” altogether, one whichdoes not omit any portion or aspect of the originally recorded ECGHolter data. Instead of destructive fast play back of the tape anddigital compression of the Holter data, CVAT improves the dynamic rangeelectronically prior to slowly encoding the whole, unmodified analogsignal using the highest possible sample rate and quantization. CVATdecodes the digital file into an optimum analog display which itself canbe visually compressed, magnified at will and processed withoutsuffering any loss, but rather being enhanced by various differentprocesses which are made available by CVAT and its related software. Inaddition, the only limits containing further development and refinementof the CVAT process are those temporarily imposed by the ephemeral andupwardly spiraling limits of computer and signal analysis technology.The CVAT process remains an infinitely upgradeable, high-quality systemwhich takes Holter analysis orders of magnitude beyond currenttechniques.

[0024] Referring now to FIG. 1, there is shown a exemplary Holterelectrocardiogram. The P wave is the ECG representation of the atrialdepolarization which cause its contraction. PQ is the segment betweenthe P and the Q; it represents the delay of the electrical wave ofdepolarization at the atrioventricular node to allow the contraction ofthe atria and fill the ventricles before the latter depolarize and expelblood into the body. Ta (a microvolt shift in the PQ not present in thisfigure) is due to abnormal atrial repolarization caused by ischemia. TheQRS is the ECG representation of ventricular depolarization which causeventricular contraction. The ST segment represents the initialrepolarization of the ventricles. The ascending limb of the T waverepresents epicardial (outer surface of the ventricle) repolarizationwhich changes into endocardial (inner surface of the ventricle) andmesocardial repolarization at the apex of the upright T wave.Ventricular repolarization is complete when the T wave returns to theisoelectric line. Several different morphologies of the T wave areassociated with non-homogeneous repolarization, a sign of myocardialcell hypoxygenation and risk for lethal arrhythmia. TP is theisoelectric segment between the offset of the T and the onset of the Pwaves. TP must be considered as the isoelectric line when Ta is present.The second beat is a premature depolarization characterized by abnormalQRS and T morphology as well as greater voltage and duration than thenormal beats.

[0025] Experts in non-ambulatory electrocardiography do visual analysisof the 12 lead ECG using 10× optical magnification for which specialtracings are taken at two or four times the normal paper speed (i.e. 50to 100 mm per second paper speed) with at least twice the electricalgain (i.e. 1 millivolt inscribing a 20 mm deflection). The tracings aredone using good quality, well maintained and well-calibrated stationaryelectrocardiographs. The best examples of this art are in research donein Scandinavia. There is a pressing need to apply similar or better careto the processing and analysis of the ambulatory electrocardiogram.

[0026] Norman J. Holter Ph.D. created Holter technology usingradio-transmitted electrocardiograms in the 1940's. The method was usedfor diagnosis of arrhythmia. The first algorithms for computer assistedanalysis were designed to detect and classify premature or aberrantbeats for the diagnosis of arrhythmia. Attempts to automate detection ofmyocardial ischemia started in the early 1970's. Systems to do HolterECG processing and evaluation are well known as disclosed in U.S. Pat.Nos. 3,229,687; 4,006,737; 4,098,267; 4,183,354; 4,211,238; 4,316,249;4,333,475; 4,336,810; 4,633,881; 4,667,682; 4,883,065; 4,989,610;5,205,295; 5,398,183 and 5,433,209.

[0027] Automated evaluation of ST segment shifts was attempted with onlyminor modifications of the basic signal processing and algorithms usedfor arrhythmia detection. The ischemia algorithm compares the voltage atone 8-bits point in the ST segment (located 60 to 100 millisecondsbeyond the J point—the junction of the QRS and the ST segment) to thevoltage at another 8-bits point on the PQ taken as the isoelectric line.Correction for presence of Ta (atrial ischemia) is unheard off in thecurrent art, since it is unable to visualize this subtle but importantchange. Hence, in the current art, the ST segment (a line and, as such,defined by at least two points) is represented by a single point. Theanalytic paradigm and totally obsolete limitations in computertechnology imposed this major source of false negative reports.

[0028] Identification of the isoelectric line in the ECG is of paramountimportance for detection of atrial and ventricular ischemia as well asfor evaluation of the QT segment and T wave changes indicative ofabnormal repolarization and arrhythmogenic risk.

[0029] Current Holter algorithms can not detect ECG signs of abnormalrepolarization in a reliable and reproducible manner. Ischemic events,represented by ECG signs of abnormal repolarization and depolarization,are usually unexpected and transient. Abnormal repolarization isvisualized as microvolt shifts in the PQ segments (Ta) if atrial or STsegment and T wave if ventricular. In the current Holter art, Ta isundetected and mistakenly chosen as the isoelectric point. This falseisoelectric point and spill over of the Ta negative voltage into the STsegment are common pitfalls that introduce error in ischemia detectionby current algorithms. Down shift of the ST by Ta depends on the degreeof atrial ischemia, the heart rate, atrioventricular conductionvelocity, etc. CVAT can easily recognize such problems and use the TPsegment, instead of the PQ, as the isoelectric reference line. The TPsegment is inscribed from the end of the T to the beginning of the Pwaves in two consecutive beats. CVAT can also identify the influence ofTa into the ST segment and discriminate false positive up sloping STdepression (starting from a depressed J point) from up sloping STdepression likely to be due to ventricular ischemia.

[0030] The prior art taught by conventional Holter monitoring systemscannot retrieve, store, display or analyze high fidelity signals in themicrovolt or microsecond range. Fast magnetic tape play back donewithout optimizing the dynamic range, scanty sampling, poor quantizationand extreme data compression deteriorate and diminish the signal.However, computer memory (1.2 Megabytes) and processing time are savedand telephonic transmission of a scanty, low fidelity, low resolution,low dynamic range signals file is facilitated. Fast FourierTransformation and other algorithmic manipulations are used to automateprocesses, reduce operator time and level of skill, speed analysis anddecrease cost. All the above contribute to the poor diagnosticperformance of current Holter technology for conditions other than grossarrhythmia.

[0031] The present invention (CVAT) preferably uses: the best possibleelectronic technology for integral signal recovery with preservation andenhancement of the dynamic range, fidelity, time and voltage resolutionof biologic waves encoded in any recording media; the best possiblecomputer and signal analysis technology to digitize the analog biologicsignals for storage, further enhancement, and archival preservation ofthe signal; and the best possible electronic, computer and signalanalysis technology for the recovery, display and evaluation of thesignals for basic research, medical and veterinary diagnosis.

[0032] Ambulatory electrocardiography done according to the Holtertechnique was used for the initial testing of the CVAT method andsystem. CVAT can be used in research, clinical practice and massscreening as an aid to diagnose cardiovascular conditions which include,but are not limited to: 1) Myocardial ischemia in all it's forms; and 2)Repolarization (including but not limited to QT prolongation andelectrical alternans) and depolarization heterogeneity as signs ofincreased cardiovascular risk.

[0033] The instant CVAT invention enables extension of Holter monitoringanalysis to the detection and interpretation of ECG signals at andbeyond the microvolt and micro second range. These minute changes encodeimportant diagnostic and prognostic information not discernible fromcurrent Holter techniques or other forms of electrocardiographicanalysis. Conventional Holter monitoring and ECG systems cannot detect,preserve or recover signals at or beyond the microvolt or microsecondrange. Exception is made of techniques limited to the electrophysiologylaboratory not applicable to mass screening or daily clinical practiceoutside of specialized centers.

[0034] The CVAT invention provides a method for biologic signal analysisby trained but not medically skilled technicians. Cost effectiveprocessing is aided by a variety of well identified morphologic patternsobtained by visual compression, in the X (time) axes of the played backsignal. The visually compressed patterns are highly suggestive orpatognomonic of important electrocardiographic changes which areconfirmed by examination of the expanded ECG tracing.

[0035] The purpose of algorithms in current use is to provide an ECGevaluating system, as automated as possible, which scans the tape asfast as possible with minimal or no operator interaction. Undue relianceis placed on a physician over reading of very small depictions of lowfidelity greatly deteriorated ECG tracings recovered from the digitalfile. Unless the over reader reviews the whole analog signal encoded inthe original recording media (in addition to editing the computerfindings), ischemic and other events missed by the computer can not bedetected. This is the most common and potentially fatal shortcoming ofthe current Holter art. Visual examination of the analog recording isexceptional; it is done only in very few research centers and not byHolter analysis services that support clinical practice or research ingeneral.

[0036] Current computerized Holter analysis algorithms use heartbeatsuperimposition and template-matching schemes to recognize departuresfrom normal. Which beats, in a pool of about 100,000 in 24 hours, arethe norm for a patient? This is a basic problem which has to be dealtwith even when neural networks, used in research only, select beats to“train” the computer to recognize “normal” beats. After digitalconversion, each heartbeat becomes a series of digital valuesrepresenting XY points of the waveform at various intervals. In currentHolter analysis the number of digital points per heartbeat is, at best,33 or lower if the heart rate goes above 60 beats per minute. Thecomputer does beat matching to evaluate the difference between values atvarious points of the waveform and to compare such values withcorresponding points of templates. A match is defined as any sum of theabsolute value of each of the differences within a preset range. Theclosest match is called the matching template. If no template matches,the operator must classify. The degraded signal preserved by the currentart allows only the grossest matching which cannot go beyondidentification of largely aberrant beats. In addition, currentalgorithms include software to analyze the series of waveforms accordingto a nondeterministic logic state analysis. This analysis permits thesystems to indicate when waveforms correspond to ventricular ectopy(VE), bigeminy, VE pair, and ventricular tachycardia, only.

[0037] A standard waveform has a P wave, a QRS complex and a T wave. Asit is well known in the prior art, the QRS complex is generallyidentified by its major peak, usually the R wave. The T wave is thenidentified as the first peak after the R wave. A T wave template is usedto process the wave quickly and inadvertent recognition of a T wave asan R wave is minimized but still exists. The T wave template is aclassification that the operator may apply when asked to classify the‘beat’. Thereafter, any peak that matches the T wave template is totallyignored, as though no peak had been found at the position. If theoperator incorrectly classifies a T peak that is or looks like a realbeat, that type of beat will be ignored. Therefore, the method is usedas a last resort, when setting the other parameters does not help, whichcan occur with patients who have peaked T waves. Peaked T waves are acommon early manifestation of ischemia. Whenever the ST segment shiftsup or down due to myocardial ischemia, the T morphology is usuallyabnormal and not amenable to template classification. While templateswork well for arrhythmia, over reliance in abnormal beat classificationusing predetermined templates is a reason for the poor performance ofcomputer automated Holter analysis in the diagnosis of conditions otherthan arrhythmia.

[0038] The template matching method is probably good enough forventricular and other gross forms of arrhythmia, which manifestthemselves by millivolt range changes in the QRS. Howeversuperimposition of fast played back, scantily sampled, mercilesslycompressed, filtered, smoothed and/or Fast Fourier Transformed beatscannot be trusted, since it processes a signal different from thatoriginally encoded in the magnetic tape. Template detection may beconvenient, but applied to a digital file which lacks integrity, dynamicrange, fidelity and resolution, it cannot be sensitive or specific norcan it detect abnormalities in microvolt regions such as the PQ, STsegments or the P and T waves.

[0039] The sophisticated cardiology community is aware of the currentHolter analysis shortcomings; hence, this method is not routinely usedas an aid in the diagnosis of highly lethal cardiovascular risks.

[0040] The following passage is taken verbatim (bolding added) from U.S.Pat. No. 5,398,183 issued on Dec. 10, 1990. This algorithm is widelyused in patient care and research and further demonstrates thedisadvantages of current Holter processing techniques.

[0041] “As another feature of the invention, a full disclosure filerepresenting the entire series of waveforms on the tape is generated.The file comprises compressed data of limited resolution and limitedsampling rates. The original data is reduced in resolution by skipping,averaging, or otherwise “decimating” samples, only using samples at arate near 33 samples per second with reference to the patient data.(This is an equivalent rate of 33 samples/sec. of the data generatedwhen the patient was originally monitored by the analog Holter monitor.

[0042] Of course, the data reading rate off the tape is much faster.) Inthis system 100, this is accomplished by averaging 4 samples, or bypicking one out of every fourth sample. The data is scaled in amplitude(and limited) so that the total excursion is 32 levels. The 32 levelsare sufficient resolution to plot on a laser plotter at 200 dots/inch,producing a 0.15″ tall waveform. The sample frequency (referenced topatient) is sufficient to see all R-peaks of normal beats by position,and to display the waveforms of ventricular beats sufficiently clearlyto be identified. The data is then further compressed by using a seriesof coding steps. First the data is converted to differential coding.(This is a version of DPCM, ‘Differential Pulse Code Modulation’ in thetelecommunications industry). Each sample has the previous samplesubtracted from it (as the example in FIG. 7 shows). This is a simple,and computationally efficient means to produce codes which consistmostly of the smaller integers near 0. In fact, the output will oftenhave runs of 0s, or +1s, 0, and −1s. Less frequently the differenceswill be larger numbers (6 to 31), mostly near the R peaks. Thedifferential output is limited to the range −31 to +31. The data is thenencoded further using a variation of ‘Huffman’ coding, or other codeswhich use few bits for symbols which occur frequently, and more bits forsymbols which occur infrequently. (The symbols to be coded are the 63integers in the range −31 to 31). This may be combined with run lengthcoding, which is the coding of a repeated sequence of the same symbolwith a code representing the sequence in fewer bits than repetitions ofthe code representing the symbol singly. The result of this coding is tobring the number of bits to represent a data point down to around 2 to 3bits. This typically allows 24 hours of data to occupy less than 1megabyte, where a byte is 8 bits. (3/8 byte/sample*33 sample/sec*60sec/min*60 min/hr*24 hr/tape=1.07 Megabyte/tape). This allows the fulldisclosure to typically be stored on a single IBM PC compatible 1.2Megabyte diskette, or transferred by telephone in 10-20 minutes usingthe new 9600 Baud Modems.”

[0043] “Taking every third sample provides a limited sampling rate andscaled differential coding provides limited resolution. Furthercompression, such as run length and Huffman coding, may then be used sothat the full disclosure file can be even further significantly reducedin size. The differential values 0, +1, −1, +2, −2 may be seen to occurmore frequently than the larger values of 6 to 31 and −6 to −31. If thesmaller integer values are represented by codes using two or three bits,then the size of the file can be further reduced. FIG. 8 is an exampleof a part of a limited resolution, full disclosure file recreated fromdifferentially encoded, compressed data. The circled areas indicateventricular ectopy and supra-ventricular ectopy which is clearlyrecognized even though this portion of the file was created fromcompressed data.”

[0044] The best resolution to be expected with the algorithm describedin this patent are 33 points in the X axes and 32 points in the Y axesto inscribe one heart beat if the heart rate is 60 beats per minute. Ifthe heart rate goes to 120 per minute there will be, at best, 16 pointsto describe the whole cycle length.

[0045] After the “decimating compression” it is only benign to say thatthe algorithm driven file will have poor resolution and fidelity. A24-hour Holter recording is housed in 1.2 Megabytes, and yet a 3-minutesong, reproduced with any decent degree of fidelity, takes about 30 to40 times the memory currently allocated to a 24 hours Holter recording.This is a grave problem that needs immediate redress. In contrast, CVATencodes the same 24 hours Holter recording in about 350 megabytes. TheCVAT file improves the dynamic range and preserves the integrity,fidelity and resolution of the signal recorded. It is not surprisingthat the quality of the ECG recovered from current Holter analysisalgorithms is too poor to identify anything but arrhythmia with somedegree of certainty. The substantial difference made by CVAT'spreservation and enhancement of the signal has been demonstrated in aretrospective study done comparing CVAT with the best current algorithmanalysis. The results of this study are provided below.

[0046] The passage below., taken from the U.S. Pat. No. 4,989,610 issuedon Feb. 5, 1991, illustrates problems in another crucial point ofcurrent Holter analysis (bolding added).

[0047] “The first step in this portion of the program reads the sixitems contained in the beat time log (BTL) for a particular beat 1220(see FIG. 55). The data in the BTL is 16 bits wide. It includes the binnumber (to be assigned by the binning operation (BIN#)), a 32-bit numberindicating the time of occurrence of the beat in terms of 1/120 secondsamples of time (BTH and BTL), a TEMP location for temporary storage ofdata, a FLAG word, an 8-bit ST measurement, and an 8-bit ST-slopemeasurement.”

[0048] “The data representing one channel of the present beat consistsof thirty-two samples. The tenth sample corresponds to the location ofthe R-wave, as determined by the beat detection software. Nine samplespreceding the location of the R-wave and twenty-two samples immediatelyfollowing the location of the R-wave constitute the remainder of thesamples.”

[0049] “Then, the DSP chip 300 performs the Fast Fourier Transform (FFT)on the thirty-two samples of the channel 1 data, producing sixteen pairsof real and imaginary data.”

[0050] “The pattern describing the members of this first bin are thetwelve points in the complex plane 1236, with each point beingassociated with either channel 1 or channel 2 and with one of the sixfrequencies. The six pairs of numbers that describe the pattern for thesecond and following beats are compared, according to their channel andfrequency, with the groups of points that defines the bins already inexistence. If the twelve points characterizing the morphology of a beatwhose bin is being determined are sufficiently close, on apoint-by-point basis, to the twelve points of an already existing bin,that beat may be associated with that bin. If the twelve pointsdescribing the morphology of a present beat do not come sufficientlyclose to all twelve points describing all already-existing bin, a newbin is defined. The twelve points defining the new bin are the twelvepoints characterizing the morphology of the most recent beat. The twelvepoints describing a beat need not match precisely with the twelve beatsdefining a bin for the beat to possibly be placed in the bin. The twelvepoints describing the morphology of the beat are sufficiently close tothe twelve points defining the bin if each of the twelve points fallswithin windows centered on the points defining the bin.”

[0051] The passage teaches that 32 samples represent a heartbeat in eachchannel and that these samples are subjected to Fast Fourier Transformto generate “sixteen pairs of real and imaginary data”. These sixteenpairs of “real and imaginary” data cannot be expected to fully describethe complex morphology of each heartbeat. With this algorithm, all themicrovolt nuances will certainly be irretrievably lost. These briefpassages provide strong reasons to render this algorithm useless foranything but arrhythmia detection.

[0052] The current automated systems for Holter analysis retrieve only asmall portion of the analog signal. Excessively fast play back speed ofthe tape, low sampling and quantization rates, “lossy” and drastic datacompression, Fast Fourier Transform to interpolate imaginary data,filtering, smoothing, etc. are done to accommodate the need for verysmall data files suitable for telephonic transmission and automatedanalysis. The price paid is extremely poor ECG data unsuitable forrecognition of ischemic and other dire electrocardiographic signs withany degree of certainty.

[0053] Myocardial ischemia is the result of oxygen debit in the heartmuscle and conduction system due to increased demand or decreased supplyof oxygen which cannot be fulfilled because of: 1) organic, fixed,coronary artery stenosis such as that seen in patients withatherosclerotic plaques in the luminal wall of their coronary arteries;2) functional, episodic, often unpredictable constriction of normal oratherosclerotic coronary arteries; or 3) clot formation over anatherosclerotic plaque.

[0054] Although spasm was historically suspected to be a cause ofcoronary occlusion, from the 1940's to the 1960's the common wisdom wasthat atherosclerotic arteries were unable to constrict. In the 70'sexperts in the field demonstrated that atherosclerotic plaques aremostly eccentric with a small free arterial wall (opposite to theatheromatous plaque) likely to cause total occlusion when minor spasm ofsuch small free wall occurs. When coronary artery spasm happens, gapsbetween the endothelial cells happen, collagen protrusion inducesplatelet aggregation and in-situ clot formation. Thrombosis can alsolead to partial or total occlusion following the arterial spasticepisode.

[0055] Fixed, organic, atherosclerotic arteries can be readilyidentified. The conventional 12-lead electrocardiogram can disclosepatognomonic signs of permanent (not episodic) ischemia of the heart.The 12-lead electrocardiogram is not expected or designed to detecttransient and unpredictable episodes of myocardial ischemia orarrhythmia since it depicts only 3 of the 100,000 or more heart beats wehave in 24 hours. For detection of sporadic arrhythmic or ischemicevents, usually triggered by diverse stressful stimuli of daily living,properly done Holter recording is the only available method,electrocardiographic or otherwise.

[0056] Permanent (not episodic) myocardial ischemia due to fixedcoronary artery occlusion can be detected by several methods other thanHolter. Electrocardiography and or echocardiography done duringstandardized exercise challenge can detect ischemia and/or arrhythmiainduced by physical stress. Other, more invasive methods, such as druginduced stress testing (the pharmacologic induction of increased cardiacoxygen demand by administration of drugs which elevate the heart rate),nuclear radiology or cardiac catheterization, are designed to detectfixed coronary artery occlusion.

[0057] All methods available today, other than the Holter technique, areunable to detect myocardial ischemia due to transient spastic and/orthrombotic causes of decreased coronary blood flow. Coronary arteryspasm frequently happens without preceding elevation of the heart rateand/or blood pressure and is commonly triggered by neurohormonal,emotional and/or environmental (e.g. exposure to cold, second handsmoking etc) factors, not inducible in controlled cardiovascularlaboratory circumstances. Hence, this grave condition escapes detectionunless Holter recordings are done under the fleeting and often difficultto identify forms of daily life stress that induces the attacks in agiven patient. The current Holter recording equipment has enoughfidelity to detect these episodes. The limiting factor is the currentcomputerized Holter analysis that is unsuitable for detection ofanything but gross arrhythmia. The current art suffers from falsenegative findings which have dire consequences for patients consideredhealthy when they are not. Today, the only reliable method to analyzeHolter recordings for ischemia is the direct visual inspection of theanalog tape by a competent electrocardiographist. Such visual Holteranalysis is time consuming and hence, done only in few research effortsand not cost effective or applicable to daily clinical practice or massscreening.

[0058] Computerized Holter analysis was designed for the detection ofarrhythmia, and has remained essentially unchanged. Arrhythmia inducesgross changes in the time and voltage domains of the recording.Algorithms to detect arrhythmia rely on large, millivolt range.Ischemia-induced abnormalities are in the microvolt range and areunlikely to stand the decimating affects of current algorithms devotedto minimize file size. Norman J. Holter, Ph.D. originally designed hisvaluable method and technology (U.S. Pat. No 3,229,687. January 1966.Holter et al.) for the study of heart rate and rhythm. The minor changesintroduced by computer algorithms are not sufficient for reliabledetection of ischemia or risk for potentially lethal arrhythmia.

[0059] In cardiovascular diagnosis, it is important to monitor the levelof the ST segment of the heart beat signal since the amplitude anddirection of the shift correlate well with the oxygen balance in thepatient's heart. A heart receiving insufficient oxygen experiencespredictable anomalies in the ST segment called “ST Depression” or “STElevation”. The names relate to the directional shift (negative orpositive microvolts in reference to the isoelectric line) and shape ofthe ST segment of the ECG waveform during periods of insufficient heartoxygenation. The magnitude and morphologic changes of the T wave areadditional indicators of ischemia which the current algorithms areunable to, detect. The CVAT method makes full use of morphologic changesin all portions of the ECG to aid in the diagnosis of ischemia andarrhythmia risk.

[0060] The normal ST segment is located at the isoelectric level whichusually aligns with the PQ or TP segments. PQ segment shift isfrequently due to artifacts or ischemia of the atria (Ta). The normalcondition is generally referred to as the “isoelectric alignment” of theST segment. ST segment shifts, measured in microvolts, above or belowthe isoelectric line are a reflection of abnormal myocardialrepolarization due to inadequate oxygenation of the heart. Ischemia notfelt by the patient is generally referred to as “silent ischemia”, whileischemia which is painful is called “angina”. All or most ischemicevents may be. silent. Frequently 80 to 90% of the ischemic episodes canbe asymptomatic or have uncharacteristic manifestations known as anginaequivalents. However, silent or symptomatic, ischemia can equally inducearrhythmia, myocardial infarction or sudden death. It is suspected thatsilent ischemia is the underlying problem in the 50% of patients whohave myocardial infarctions or die suddenly without having had anypremonitory symptoms or signs.

[0061] It is very important to identify the isoelectric line and thelevel of the ST segment in the patient's normal heartbeats in order tobe able to properly identify departures from normality. U.S. Pat. No.5,433,209 issued on Jul. 18, 1995 includes the following passage (notdirect quotes and bolding not in the original document):

[0062] For each ECG signal channel, the QRS peak location isapproximated from the point at which a beat is detected over a beatdetection threshold. Then, the ST algorithm backs up 10 samples from thepeak of the QRS complex to approximately land on the PR interval of thebeat wave form. Next, a region of “minimum activity” is located and thebaseline offset, identified as “Base Corr (i)”, is found. The “minimumactivity” region is found by finding the smaller of the two 3-pointabsolute value derivatives in a 5 sample window on the PR interval. Thebaseline offset is taken for the sample which is located 30 samplesforward of the QRS peak which is thereafter identified as the STsegment. The baseline offset at the region of “minimum activity” issubtracted from the sample value at this point and the difference,measured in millimeters, is taken to be the ST level. Each time a STlevel is calculated, a last eight beats ST level average is alsocalculated. Each ST level average during the minute is compared to thelast eight beat minimum and maximum ST level average to find the minimumand the maximum eight beat average for the minute. Hourly and monitoringperiod minimum and maximum ST levels are also determined in the abovefashion. ST level sums are also maintained in the minute summaries, hoursummaries and the end of monitoring period summary, with thecorresponding normal beat counts. The minute ST level averages arecalculated by dividing the minute ST level sum by the normal beat countsduring the minute. The hour ST level averages are also calculated in asimilar fashion. The minimum, maximum, and average ST levels are eachstored as a signed byte of information. Each value is used along withthe gain set for each channel and the analog to digital range set foreach channel in order to calculate the ST depression or elevation value.Since, the ST averages all require extensive computations, thecomputational load is spread over several periodic interrupt cycles.Minute ST level averages are monitored over the entire monitoring periodto determine an ST “episode”. An “episode” is detected if the minute STlevel average in any channel is at least less than −1.0 mm and issustained at this depressed level for more than a minute. ST episodes ofless than −1.0 mm, −2.0 mm, and −3.0 mm and their duration time inminutes are recorded.

[0063] All these intensive computational niceties are done on a digitalfile known to be incomplete and with major fidelity, resolution anddynamic range deficiencies. Hence, it is not surprising that currentalgorithms miss 9 out of 10 patients whose ischemia can be identifiedwith visual analysis.

[0064] In the current practice of cardiology, the goal of therapy forpatients with coronary artery disease is being upgraded from simplycontrolling anginal pain to a more rational and forward lookingreduction or elimination of silent and symptomatic ischemic episodes.Any form of ischemia, symptomatic or not, short or long can kill orinduce myocardial infarction. Properly done, the Holter method is theonly way to detect silent or atypically symptomatic ischemia and has toplay an increasingly important role in the management of this seriouscondition. To play that important role in the detection and monitoringof ischemia the current Holter art risk of false negative analysis mustbe eliminated. Biologic signal analysis can and should make a quantumleap using, electronic technology, hardware and software developmentsachieved in the last decade.

[0065] Sudden cardiac death (SCD) claims over 350,000 lives annually inthe United States; 50% of which had no premonitory symptoms or signs.SCD usually follows an abrupt disruption of heart rhythm primarily dueto ventricular fibrillation. Fibrillation occurs when transient triggersimpinge upon an electrically unstable heart causing normally organizedelectrical activity to become disorganized and chaotic. Complete cardiacdysfunction results and may end in sudden death. An episode of pooroxygenation of the heart (myocardial ischemia) is probably the mostfrequent cause of ventricular fibrillation and death.

[0066] A major, and as yet elusive, objective of preventive cardiologyis to detect patients at risk for catastrophic arrhythmic cardiacevents, including sudden cardiac death. Methodology used to identifysubjects at risk must be improved. Electrical alternans is theelectrocardiographic manifestation of heterogeneous myocardialrepolarization and depolarization. Electrical alternans and ischemia areprominent indicators of risk factors for major catastrophic or lethalcardiac events. Gradual microvolt changes are seen in the ST segment andthe T wave and are not as abrupt as the onset of abnormal QRS. Microvoltsignals are easily obliterated by poor dynamic range, “decimating”compression algorithms, creation of “imaginary” points, etc used byalgorithms in the quest for automation and trans-telephonic transmissionof minimized Holter files.

[0067] Cost effective, non-invasive, techniques for mass screening andidentification of individuals at risk for catastrophic cardiac eventsthat affect close to 2 million persons per year in the US alone areneeded. Diagnostic technology must be constantly revised to make fulluse of the ever improving developments in electronics as well ascomputer hardware and software. Prompt risk detection, will lead toimmediate confirmatory diagnosis, interventional cardiaccatheterization, coronary artery by-pass, pharmacologic management,etc., thereby allowing the saving of hundreds of thousand of lives inthe world. There is need to develop an improved Holter analysis that canbe cost effective in time and level of operator skill and still preciseenough to avoid potentially catastrophic false negative reports.

[0068] Advent of Holter analysis as a reliable method to detect ischemiaand risk for severe arrhythmia will also facilitate targeted new drugdevelopment by providing valid objective therapeutic end points, insteadof unreliable surrogate end-points. Cutting age technology has to beused to preserve the fidelity, dynamic range, time and voltageresolution of the recorded signal, a step of paramount importance forthe accurate diagnosis of electrocardiographic abnormalities in themicrovolt region. Holter analysis obsolescence is the medicalcounterpart of the Y2K problem with the difference that it's cost inmortality and morbidity is orders of magnitude greater than the Y2K canever be. This problem is greatly reduced, if not completely solved, bythe teachings of the present invention.

[0069] The use of the instant invention to process analogelectrocardiographic signals makes it possible to evaluate every singlebeat of the ambulatory electrocardiogram by compacting the signal in amanner that will disclose sui-generis visual patterns which correspondto and readily identify classic, discrete anomalies of theelectrocardiogram, described by experts in the field as part ofpathologic conditions compromising the cardiovascular system. Theunderstanding of these patterns make it possible to identify theabnormal elements of the electrocardiogram..

[0070] The immediate value to mankind provided by the instant inventionis that it makes possible identification in a non-invasive andcost-effective manner, patients who have silent myocardial ischemia andhence are at high risk for myocardial infarction, sudden death and othercatastrophic events. About one half of patients with myocardialinfarction, sudden death, lethal arrhythmias, etc. are patients who haveno history of coronary heart disease and are probably carriers of silentmyocardial ischemia, which triggers the terminal events leading to thepatient's demise. The instant invention enables timely discovery of thiscovert condition and enables timely anti-ischemic therapy which willresult in the saving of millions of lives as well as a decrease inhospital use, disability and improvement of the quality of life of thoseaffected by silent ischemia a potentially lethal condition.

[0071] As explained in detail above, instead of visual analysis,computer programs implementing mathematic algorithms are presentlyroutinely used to perform analysis of electrocardiograms in an attemptto detect abnormalities therein. Such computer programs have had onlylimited success in diagnosing pathological conditions which compromise apatient's cardiovascular system. Due to their cost-effectiveness,however, such mathematical techniques are widely used today. As aresult, many patients have had pathological conditions go undetected.

[0072] Thus, a need exists for improved methods and systems which enableimproved detection of pathological conditions during analysis of theelectrocardiogram and other waves of biological origin.

[0073] The instant invention advantageously uses algorithms and computerprograms created for the purpose of editing, manipulating and/oranalyzing sonic and/or electromagnetic waves, such as music processingprograms.

SUMMARY OF THE INVENTION

[0074] A primary object of the instant invention is to increase theaccuracy and decrease the cost of biologic signal analysis for use inmass screening, clinical practice and research.

[0075] The instant invention, referred to herein as, the ComputerizedVisual Analysis Technique or “CVAT”, generally relates to the use ofup-to-date signal processing technology with state-of-the-art electronicand computer technology for the evaluation of biologic signals obtainedfrom isolated cells, tissues, human and animal species to aid basicresearch and diagnosis of medical and veterinary disease states. CVATcan be used to process biologic signals such as, but not limited to:

[0076] The electrocardiogram in all it's forms, and in particular, thecontinues electrocardiographic signal such as that obtained with theHolter technique or during on-line, real time monitoring of a patient.

[0077] The electroencephalogram

[0078] The myogram

[0079] The phonocardiogram

[0080] Respiratory sound waves including their correlation with theelectrocardiogram and encephalogram to diagnose sleep disorders in thehospital and in out of hospital settings, etc will be evaluated.

[0081] The invention also enables the generation of a report of theevaluation and the triggering of alarms in the real time monitoringmode.

[0082] CVAT is different from current forms of biological signalanalysis in that it preserves the integrity of the analog signal,enhances dynamic range, the fidelity and resolution of the originalsignal obtained. All these features lead to better interpretation of thesignal using compressed visual patterns, which, in turn, leads to quickand easy identification of abnormalities suggestive of pathologicstates. CVAT is based on the application to biological signal analysisof advances made in the software, hardware and electronic technologyused to process and analyze sound waves. This is a major departure fromcurrent obsolete ways to digitize analog signals, which include the useof extreme lossy digital compression, Fast Fourier Transformation andother mathematical and autocorrelational engineering based algorithmswhich markedly deteriorate the quantity and quality of the signal to beevaluated.

[0083] A main application of the present invention is to improve theanalysis of the Holter electrocardiogram. The invention departs from thecurrent Holter ambulatory electrocardiogram analysis in that it replacesauto-correlational communications engineering techniques andquantification-dependent analysis of the electrocardiogram done withobsolete computer technology which eliminates most of the originalsignal and distorts the fidelity, resolution and dynamic range of thesmall fraction kept in the digital file for algorithm driven analysis.

[0084] Instead, CVAT relies on morphologic and pattern evaluation signalanalysis complemented with quantification when necessary. The totalityof the signal originally recorded is preserved with protection andenhancement of dynamic range, resolution and fidelity of the signal.

[0085] The following features represent the main aspects of the instantCVAT invention, and together enable the invention to provide optimalprocessing and analysis of biologic waves:

[0086] Prior to analog to digital conversion, each lead of the ECG orother biologic signal undergoes electronic enhancement of the dynamicrange;

[0087] Analog to digital conversion is done with the best possibleequipment and the slowest possible play back speed of the originallyrecorded signal;

[0088] An optimum quality sound card is used for analog to digitalconversion using the highest possible sample (preferably 44,100 Hz persecond per channel or higher) and quantization (preferably 16-bits persample per channel or higher) rates;

[0089] Digital sound processing software and techniques are used for theprocessing and analysis of biological signals. The inventor hasdetermined that one suitable sound processing software is SOUND FORGE,which is designed for processing digital audio. Other similar softwareprograms (such as, but not limited to seismographic and geologicsoftware) used for wave analysis may also be used in accordance with thepresent invention. Such software allows various steps to be performed toenhance the signal (without introducing distortion) in the voltage andtime domains and enhances pattern visualization and other forms ofanalysis;

[0090] The invention preferably used file formats originally created forsound wave applications (such as, but not limited to .wav and othersimilar file extensions) to process the biological signals;

[0091] Computer sound cards (such as but not limited to the Montego Baycard) are used to code and decode the analog biologic signal;

[0092] Visual compression of the analog signal is used to display thesignal with high fidelity, resolution and dynamic range to identifyvisual patterns used as indicators of abnormalities which can beconfirmed by expanding the signal;

[0093] Use of visual pattern libraries to train technicians with lowlevel skills to facilitate the cost effective use of CVAT for massscreening, clinical practice and research;

[0094] Use of time interval measurements in the biologic signal to assesinternal functional harmony as a reflection of normality or pathology.Such time intervals can be measured with a precision at or below10,000^(th) of a millisecond and will be even more reliable when betterrecording techniques are introduced. Normal standards applicable to themethod used will be created to replace normal values extrapolated fromdata obtained with better equipment and in different circumstances.Extrapolated quantitative-standards lack precision; and

[0095] Use of screen capture software (such as, but not limited to,Paint Shop Pro) to document the findings of the analysis and to transferthe images to graphic processing programs (such as but not limited toAdobe PhotoShop). This software is used for magnification andpreparation of the report of the analyses.

[0096] In accordance with another aspect of the invention, internalharmony in the duration of different intervals of the electrocardiogramis advantageously used, and relies more on relative than on absoluteduration. Internal harmony is done to evaluate repolarization of themyocardial cell according to the relationship between:

[0097] Cycle length duration measured as the J-J interval

[0098] Total duration of ventricular repolarization measured as J-Te andrelated to cycle length as (J-Te/J-J)×100

[0099] Transmural repolarization time measured as Tp-e related to thetotal duration of ventricular repolarization as (T-pe/J-Te)×100.

[0100] In accordance with another aspect of the invention, the method isused to detect microvolt and lesser changes in the ST segment, T wave,etc., as an indication of myocardial ischemia or electrical alternans ornon-homogeneous repolarization and/or depolarization in ambulatory, costeffective conditions.

[0101] In accordance with another aspect of the invention, the method isused for evaluation of microvolt and lesser changes in the PQ intervalshown as Ta changes suggestive of atrial ischemia.

[0102] In accordance with another aspect of the invention, morphologicpatterns are used to detect transient or intermittent myocardialischemia when other forms of Holter analysis are useless in evaluatingrecordings with artifacts, bundle branch block, ventricular hypertrophy,previous myocardial infarctions, etc.

[0103] In accordance with another aspect of the invention, morphologicpatterns are used to detect intermittent atrioventricular orintraventricular blocks potentially caused by cardiac pathology such as,but not limited to, ischemia.

[0104] In accordance with another aspect of the invention, the method isused to detect traditionally minor (less than 1 mm shift in the currentart) considered “non-specific” ST segment shifts as sign of importantischemia risk. This is done by correlating the ST shift to the QRS aspercent of the preponderant wave of the QRS normalized to its maximumpotential using the CVAT software described herein.

[0105] In accordance with another aspect of the invention, the method isused for on-line monitoring of the electrocardiogram and other biologicsignals.

[0106] In accordance with another aspect of the invention, the method isused to analyze simultaneously obtained upper airway breath sounds andthe electrocardiogram to detect sleep apnea at home or elsewhere.

BRIEF DESCRIPTION OF THE DRAWINGS

[0107] These and other objects, features and advantages of the instantinvention will become apparent from review of the following detaileddescription with reference to the accompanying drawings, in which:

[0108]FIG. 1. Shows waves and segments of the electrocardiogram;

[0109]FIG. 2. Shows inaccuracy of the voltage calibration signal incurrent Holter recordings;

[0110]FIG. 3. Shows examples of voltage calibration differences acrossand within Holter recordings;

[0111]FIG. 4. Shows evaluation of ST segment shift as percent of theQRS;

[0112]FIG. 5. Shows calibration and voltage changes during a recording;

[0113]FIG. 6. Shows examples of voltage optimization in a recording donewithout enhancing the dynamic range;

[0114]FIG. 7. Shows an expanded view of FIG. 6 to show visuallyidentifiable electrical alternans;

[0115]FIG. 8. Shows visually compressed CVAT pattern to illustratenormal elements thereof;

[0116]FIG. 9. Shows examples of CVAT patterns compatible with ST segmentelevation and depression;

[0117]FIG. 10. Shows expanded ECG showing ST elevation and T wavechanges;

[0118]FIG. 11. Shows a CVAT pattern of ST depression and T waveinversion;

[0119]FIG. 12. Shows a CVAT pattern compatible with ischemia showingslow onset and offset of the ST shift;

[0120]FIG. 13. Shows expanded ECG to illustrate Ta, ST depression and Twave inversion;

[0121]FIG. 14. Shows a CVAT pattern of brief period of ST depression;

[0122]FIG. 15. Shows ST shift which becomes apparent only after voltageoptimization;

[0123]FIG. 16. Shows a CVAT pattern of ST depression and atrial flutter;

[0124]FIG. 17. Shows ST depression and atrial flutter in an expandedECG;

[0125]FIG. 18. Shows a CVAT pattern of intermittent 2^(nd) degreeatrioventricular (AV) block;

[0126]FIG. 19. Shows 2^(nd) degree AV block in an expanded ECG;

[0127]FIG. 20. Shows a CVAT pattern of ST elevation and intraventricularconduction delay;

[0128]FIG. 21. Shows intraventricular conduction delay (ICD) and STelevation in an expanded ECG;

[0129]FIG. 22. Shows intermittent, shifting ICD;

[0130]FIG. 23. Shows a P wave marching on the T wave visible throughvoltage optimization;

[0131]FIG. 24. Shows an example of resampling and voltage optimization;

[0132]FIG. 25. Shows beat to beat change on T wave morphology;

[0133]FIG. 26. Shows ST depression in the beats opposite to those inFIG. 25;

[0134]FIG. 27. Shows an example of ST depression and biphasic T waves;

[0135]FIG. 28. Shows ST depression in the recording from which FIG. 27was taken;

[0136]FIG. 29. Shows biphasic T waves;

[0137]FIG. 30. Shows Ta, ST depression and elevation in the recordingfrom which FIG. 29 was taken;

[0138]FIG. 31. Shows expanded and magnified ECG to show double hump Twave;

[0139]FIG. 32. Shows marked and quick change in T wave morphology;

[0140]FIG. 33. Shows continues tracing to show beat-to-beat changes in Twave morphology prior to a premature beat;

[0141]FIG. 34. Illustrates use of the calibration signal to find thenumber of samples per second of clock time during the recording period;

[0142]FIG. 35. Illustrates measuring cycle length in a resampled andvoltage optimized tracing;

[0143]FIG. 36. Shows expunged QRS to magnify microvolt range waves;

[0144]FIG. 37. Shows measuring of J-Te;

[0145]FIG. 38. Illustrates reason for algorithm failure to measurebiphasic T waves;

[0146]FIG. 39. Shows time conversion to measure pacemaker function; and

[0147]FIG. 40. Shows pacemaker triggered beats evaluated.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0148] As described below all the steps of the CVAT method theelectronic equipment, hardware and software used are preferably selectedand devoted to the preservation and enhancement of the dynamic range,fidelity, resolution and integrity of the biological signals beingprocessed. Compact visual analysis is done on an optimum analog signalretrieved preferably using the best possible technology. Various stepsare taken to enhance visualization and facilitate analysis to aid basicresearch, medical and veterinary diagnosis. The quantity and quality ofthe signal is protected during analog to digital conversion usingtechniques such as: 1) independent electronic channel dynamic rangemodulation; 2) slowest possible play back speed of the magnetic tape;and 3) maximum possible sampling and quantization rate.

[0149] For the same reason, digital compression, smoothing of the data,filtering, Fast Fourier Transformation etc., are preferably avoided topreserve the integrity and quality of the biological signal. The CVATmethodology, electronic equipment, hardware and software used inaccordance with the instant invention are preferably upgraded over timeto keep pace with the fast development of signal analysis electronicsand computer technology.

[0150] The following described equipment and software are preferablyused when implementing the CVAT method to process and analyze the Holterambulatory electrocardiogram.

[0151] A Denon cassette recorder model 770 R for the slow play back ofthe cassette tapes in which the 24 hr electrocardiogram was recorded.The right and left channel outputs of the cassette deck being connected(using high quality, well shielded RCA type cables) into the input jacksof a Stereo Sound Mixer.

[0152] A Radio Shack SSM-60 Stereo Sound Mixer, wherein the cableconnected to the right channel output of the Denon cassette deck is fedinto the right channel input of the CD Line 2 jack in the audio mixer.The cable connected into the left channel output of the cassette deck isfed into the left channel input of CD Line 1 in the audio mixer. Thefading slider in the Audio Mixer is preferably placed exactly in themiddle position to feed equal signals from Line 1 and 2 into the audiomixer output jack. High quality, well shielded RCA cables are preferablyused to connect the right and left channel output jacks of the audiomixer using an RCA to mini (3.5 mm) stereo jack conversion piece intothe stereophonic input of a sound card.

[0153] A high quality sound card is preferably used, such as (but notlimited to) the Turtle Beach Montego A3D 64 Voice PCI Sound Cardinstalled in a Dell mini tower. This card has greater than 90 decibelssignal to noise ratio, sampling rates as high as 96 kHz per channel at16-bit per channel digital, coder/decoder software for recording andplay back of high fidelity, high resolution, high dynamic range signals.Another sound card installed in a Gateway Solo 9100 Multimedia Notebookhas also been determined by the instant inventor to provide suitablefunctionality for use with the instant invention.

[0154] Windows 98 PC platforms are preferably used, such as a DellDimensions XPS R400 MHz PENTIUM Mini tower with MMX technology with 348MB SDRAM memory and a Gateway Solo 9100 Multimedia Notebook with aPentium MMX 266 MHz and 192 MB of RAM. It is noted, however, that anyother suitable computer platform me be used in accordance with theinstant invention.

[0155] In accordance with an important aspect of the instant invention,software dedicated or otherwise used for signal analysis of wavesincluding, but not limited to, software used in the processing ofdigital sound, seismography, identification of extraterrestrial radiowaves, etc. is advantageously used to process the biological signal. Theinstant invention is applicable to the use of all different combinationsof programming, mathematical analysis techniques, etc., devoted to theretrieval, storage, display, analysis, etc., of biological wavesindicative of the function of any and all organs or tissues, intact orisolated from human or other biologic species. Such processing ofbiological waves includes retrospective (e.g. analysis of ambulatoryrecordings of electrocardiograms or electroencephalograms), as well asreal time analysis of a stream of signals such as (but not limited to)continues monitoring of electrocardiograms or encephalograms. The CVATmethod is dedicated to preserve the integrity and enhance the dynamicrange, fidelity, resolution, and other important parameters of suchwaves.

[0156] In accordance with the invention, use of existing (and future)digital audio processing programs, such as Sound Forge XP (offered bySonic Foundry, 754 Williamson St, Madison, Wis. 53703) and all the likesound processing and editing programs are advantageously applied to theanalysis of biological waves. Sound Forge XP has been determined by theinventor to work well in connection with the method described herein.Other similar software programs for use in PC, Apple, Linux, Unix andany other computer platforms may also be used.

[0157] It is noted that Sound Forge supports an extensive set of fileformats dedicated to digital audio editing and processing. Historically,almost every type of computer platform used it's own file format foraudio data, some files are more generally applicable, and conversionsbetween almost any pair of formats is possible, but losing informationis a risk. The invention advantageously uses any of these or similarfile formats for the specific use of biological wave analysis. Examplesof some of the files which can be used are:

[0158] Active Streaming Format (.ASF)

[0159] Ad Lib Sample (.SMP)

[0160] Amiga SVX (.VSX/.IFF)

[0161] Covox V8 (.V8)

[0162] Creative Labs VOC (.VOC)

[0163] Dialogue VOX (.VOX)

[0164] Gravis Patch (.PAT)

[0165] InterVoice (.IVC)

[0166] Macintosh AIFF (.AIF/.SND)

[0167] Macintosh Resource (.SND)

[0168] MIDI SDS (.SDS)

[0169] NeXT/Sun(Java) (.AU/.SND)

[0170] Raw Files (.RAW/.*)

[0171] Real Media (.RM/.RA)

[0172] Sample Vision (.SMP)

[0173] Sonic Foundry Sample Resource (.SFR)

[0174] Sound Designer 1 (.DIG/.SD)

[0175] Sounder/Sound Tool (.SND)

[0176] Video for Windows (.AVI)

[0177] Wave (.WAV) etc

[0178] The signal analysis software is used in accordance with theinstant invention to code and decode (codec) the biological waves aswell as to retrieve, display, process and analyze biological waves forbasic research, medical and veterinary diagnosis.

[0179] The analog signal retrieved from the source is displayed, in theanalog compressed (compacted) or expanded formats, using maximumfidelity, resolution, color depth and refresh rates. A cathode ray tube(Dell Computer) as well as a liquid display system (Gateway Solonotebook) were used. Both and all-future forms of compacted orcompressed analog display of digital data in the fashion describedherein may be used whether it is from retrospectively obtained (e.g.from any recording media) or real time signals from patients, animals,isolated organs, tissues, cells, etc.

[0180] To document and preserve findings displayed on the screen, tofurther magnify the signal or subject it to image enhancement, etc., ascreen capture software program is preferably used, such as Paint ShopPro 5. Photoshop 5 may be used to process the image, enhance contrast,enter legends, further magnify etc. Microsoft Word and MicrosoftPublisher are preferably used for the preparation of reports tosummarize the findings of the signal analysis. JPEG encoded images mayinserted within the text. The above and similar programs and digitalimage files for the different processes needed for visual orinstrumented analysis, image enhancement etc of the analog signalrepresenting biological waves processed using digital sound or otherwave technology process are preferably used. The images obtained can beprinted using, for example, an inkjet Hewlet Packard Printer Model1120C.

[0181] The CVAT method of the instant invention is designed to processand analyze biological waves using digital sound or any othercomputerized wave analysis software or techniques, including but notlimited to the use of digital audio acquisition, editing, reproductionetc., as tools to facilitate computer aided visual as well asalgorithmic and mathematical analysis. The purpose of CVAT is to enhancethe use of signal analysis as an aid to basic research, medical andveterinary diagnosis. The CVAT method of the instant inventionpreferably includes, but it is not limited to, the following sequentialsteps:

[0182] Transferring the analog signal from the original media into thecomputer hard drive. This is preferably done using the best possibleelectronic equipment, enhanced dynamic range and optimum play backspeed.

[0183] Using computer software for high sampling and quantization rates(at least 44,100 Hertz at 16 bits per sample, per channel where thesampling rate is the number of frames per second), to preserve thedynamic range, integrity, fidelity and resolution of the analog signalencoded in the original recording media.

[0184] Allocation of optimum amount of computer memory to preserve theintegrity, dynamic range high fidelity and resolution of the signal.Digital compression algorithms, filtering, smoothing or any other signaldeteriorating or diminishing manipulation likely to compromise theintegrity, fidelity, resolution and dynamic range of the original analogsignal are preferably avoided at all times.

[0185] CVAT is preferably done with the high quality hardware (codecchips, etc.) and software to code and decode the analog signal torecover and display it in a high fidelity-high resolution mode in acomputer monitor at or above 1600×1200 pixels with 32-bit color and highrefresh rate.

[0186] CVAT is preferably done using a high quality computer system tomagnify waves in the X and Y-axes. Magnification along the X and Y-axesis done to allow precise measurement beyond microvolt and microsecondlevels to facilitate visual morphologic analysis in the compressed orexpanded modes. Enhanced resolution, fidelity and dynamic range furtherfacilitate detection of morphologic changes of biologic waves such asthe ECG, encephalogram, miograms, etc. Since its discovery at thebeginning of this century, electrocardiography has been a visual patternrecognition discipline. Computers can be used to facilitate such patternrecognition but in final analysis trained technicians are still superiorto computers to discriminate normal from abnormal patterns.

[0187] Use of high quality programs for screen capture and further imageprocessing of selected representative portions of the recordings is alsoan integral part of CVAT.

[0188] Each of the above-mentioned steps will be described in greaterdetail below. The caveat is that keeping pace with the fast improvementin electronic equipment, computer hardware and software, the tools andtechniques used in each step of this method will continue to improve andtranslate technologic advances to the benefit the different patientpopulations served by CVAT. For instance, 24-bit quantization as well as192 kHz sampling rates are envisioned to soon become an integral part ofthe CVAT technology.

[0189] The invention may also employ Direct Stream Digital (DSD)technology for the analysis of biological waves for basic research,medical and veterinary diagnosis. DSD uses Delta Sigma modulation togenerate a bitstream that represents the analog signal being recorded.Instead of sampling the signal at a particular instant determined by aconverter clock, the DSD converter does something quite different. Itkeeps the previous sample in memory (actually in a feedback loop, sincethe system does not record signal levels) and monitors the waveform asit continues to change. If the signal value is higher than that of theprevious sample, the converter records a one, if not, it records a zero.In this manner, full positive signals are represented by a string of 1'sand full negative signals by a string of zeros. Silence (or theisoelectric line in the ECG or EEG) is represented by alternating onesand zeros. It is not linear pulse code modulation. The density of thepulses represents the instant amplitude of the signal. Since DSD is notorganized into 16 or 24 bit samples, DSD simply records the bitstreamitself and it is and looks “analog-like”. DSD claims 120 dBsignal-to-noise ratio through what is known as noise shaping. The DSDanalog/digital converter uses 64 times oversampling achieving four timesthe density of current music CDs recorded at 44,100 Hz and 16-bitquantization. This technology will allow simultaneous processing andanalysis of up to 72 channels (signal streams) for use in CVAT analysisof electroencephalograms and 12-lead electrocardiograms.

[0190] The invention is, for example, applicable to analysis of 24 hoursambulatory electrocardiograms recorded with current art Heltertechnology. The CVAT Holter analysis aims to find classically describedelectrocardiographic signs compatible with silent, atypicallysymptomatic or symptomatic ischemia, a major cause of morbidity andmortality. Detection of Risk for lethal arrhythmias is also improved byCVAT. Ischemia is probably the most common cause of lethal arrhythmiaand sudden death. Hence, electrocardiographic signs of increased risk ofserious arrhythmia (such as depolarization and repolarizationheterogeneity and preservation of the within patient harmony of therepolarization periods) are described herein. CVAT may also be used todetect increased risk of arrhythmia and sudden death in patients withcongestive heart failure (CHF).

[0191] Cassette format magnetic tape is still the most commonly usedmedia to record the ambulatory electrocardiogram from leads attached toa patient. To facilitate 24 hr recording without changing cassettes, thetape transport speed is slowed to 1.1 or 0.55 mm (depending on themanufacturer) per second instead of the 55 mm per second used to recordmusic or other sonic waves. Differently from current Holter analysis andto preserve the quality of the analog electrocardiographic signal, CVATtechnology uses as-slow-as-possible play back speeds. As describedabove, a Denon cassette deck model 770 R that normally plays back at47.6 mm per second may be used. This model has variable play back speed.For CVAT, the slowest play back speed is preferably used at a transporttape rate of 40.4 mm per second. Hence, Holter tapes recorded at 1.1 mmper second are preferably played back at 36.7 times real time. In CVAT,slow play back speed is an important step in the preservation of thefidelity and resolution of the signal during the analog to digitalconversion of the file. The slow speed used in CVAT should be comparedto the much faster play back speeds used in current Holter analysis toaccelerate analog to digital conversion despite deterioration of thesignal quality. Current Holter analysis play back speeds between 60 and480 times real time, 240 and 480 times real time are probably the mostcommon play back speeds.

[0192] CVAT preferably uses 44,100 and 96,000 Hz-16 bits per channel asthe standard sampling and quantization rates. At 44,100 sampling rate, asingle sample is taken every 0.000023 seconds of clock time. A 24 hrHolter recording (more than 100,000 heart beats) is digitized byconventional art using, at best, 8,000 Hz samples per second followed bydrastic lossy compression schemes that reduce the digital file to about1.2 megabytes. The same file is encoded by CVAT in 350 megabytes, using44,100 Hz, 16-bits quantization and no compression schemes. This 1.2/350ratio in the richness of the digital file is a reflection of thedifference in sampling and quantization rates, tape play back speed, andthe use-no use of “lossy” digital data compression.

[0193] The sampling rates used by current Holter analysis are frozen inthe early 90's and are, at best, 8,000 samples per second of clock time.When fast play back speed is factored in, the result is about 33 samplesper second recorded time if the play back -speed is 240 times real time.In CVAT at sampling rates of 44,100 or 96,000 Hz there are 1,188 to2,376 per second of recorded time respectively.

[0194] Even the recently introduced flashcard technology is subjected tothe artificial limitations imposed by the desire to transmit compresseddata over telephone lines. An ambulatory recording system with 500samples per second, 10 bits per sample, three channels, and 24 hoursrecording, requires the storage of about 162 MB. To accommodate thisdata on a 20 MB flash memory card requires a compression ratio of 8:1 orhigher. However, the perceived need for transtelephonic transmissionlimits the flash card files to about 8-MB which require more drasticcompression schemes and/or 8-bit quantization. The signal retrieved isstill incomplete and of poor quality.

[0195] Conversion of the analog signal to digital format is a crucialstep which determines the final quality of the signal preserved foranalysis. Neither the magnetic cassette play back speed or the samplingrate undergo modulation to compensate for acceleration of the heart ratewhich are likely to happen during the recording period. The number ofdigital samples per heartbeat of the ECG can be referred to a normalheart rate of 60 beats per minute or one heart beat per second ofrecorded time. The table below compares the number of digitally sampledpoints per heart beat using current Holter analysis art at differentplay back speeds and CVAT at two different sampling rates SAMPLES PERPLAY BACK POINTS PER SECOND SPEED HEART BEAT* CURRENT 8000  240 × REAL   33 PER HB ART TIME CURRENT 8000  480 × REAL  16.6 PER HB ART TIMECVAT 44,100 36.7 × REAL 1201.6 PER HB TIME CVAT 96,000 36.7 × REAL  2615 PER HB TIME

[0196] In the time domain, at 60 beats per minute, the current Holterart has, at best, only 2.7% of the sampling points of the lowest CVATrate (33 vs 1,201 points per heartbeat). The fastest (and probably mostcommon) sampling rate used in the current Holter art has only 0.61% ofthe time points CVAT offers (16.6 vs. 2,615). Hence, starting with theanalog to digital conversion and prior to any of the other datadegrading steps, the current art deletes between 97.3 and 99.39% of thesignal encoded in the magnetic tape. The data loss increases withincreasing heart rate. If the heart rate goes from 60 to 120 per minute,only one half of the above points will be converted from the analog tothe digital format and enter the computer file. For the current Holteranalysis, this loss happens prior to further signal degradation due tolossy compression, replacement of real for imaginary points (throughFast Fourier Transformation), filtering, etc which is not the case whenCVAT is used. This data elision is compounded by the current Holteranalysis use of 8-bit instead of 16-bit cards. Quantization with 8-bitcards gives only 0.39% (256 points per channel) of the voltageresolution afforded by 16-bit cards (65,536 points per channel). Thiscalculation does not include the signal deteriorating effect of failureto do independent control of dynamic range prior to digital conversion.

[0197] The importance of quantization rate and independent channel gaincontrol for the preservation and enhancement of dynamic range will nowbe described. It is being increasingly recognized in electrophysiologyof the heart that microvolt level and lesser magnitude voltage changesencode very important diagnostic and prognostic information. Currentcomputerized Holter analysis sacrifices dynamic range, fidelity andresolution to high-speed analog to digital conversion and the need tofit the 24-hr signal in a small digital file to facilitate telephonictransmission. It is well known that lack of dynamic range affectsforemost the lower voltage changes in the signal. If dynamic range isnot optimized prior to digital encoding of the analog signal, the rangeof voltage describing points above and below the isoelectric line is notfully utilized; hence the ST-T changes in the ECG are less apparent. Aprimary difference between CVAT and the conventional art is that CVATstrives for the preservation and enhancement of the dynamic range tofacilitate identification and interpretation of microvolt and lesservoltage changes used to detect ECG signs of potentially lethalconditions. Independent channel modulation of the dynamic range, slowtape play back, high sampling and quantization rates achieve optimumstorage, recovery and display of microvolt range signals. CVAT ispreferably done with 16-bit quantization rate, but 24-bits and highermay also be used. The signal to noise ration at 16-bits per sample and44,100 Hz is about 90 dB. Current Holter analysis use of 8-bitsquantization drops the signal-to-noise ratio to 40 dB or less. Noise isknown to induces more interference in the quieter periods in music andaround the isoelectric line and the ST-T region of the ECG. Signalsmoothing and filtering done in current Holter analysis furtherdeteriorate discrimination of microvolt range changes in the signal.

[0198] In CVAT independent electronic gain control is possible becausemorphologic analysis relies on the internal harmonic relationship of theelectrocardiographic waves and relative rather than quantitative changesin the signal. Microvolt measurement in current Holter analysis is basedon numerical conversions using voltage calibration (1 millivolt=10 mmdeflection) signals which often are faulty and hence unreliable. InCVAT, independent electronic gain is adjusted in order to use the Y-axesto it's full extent with the QRS deflection as (or near) 100% of it'spotential height. This is done to expand the dynamic range and to obtainthe greatest possible benefit of the 16-bit quantization rate. Byoptimizing dynamic range prior to digital conversion, as much of thepotential 65,536 points available per channel in the Y-axes are used.High dynamic range and resolution in the Y-axes facilitates evaluationof microvolt and lesser voltage changes in the ECG. These steps areessential for the detection of ischemia and arrythmogenic risk. CurrentHolter analysis does not optimize dynamic range prior to digitizing at8-bits per sample, these results in only partial use of the 256 pointsprovided by 8-bits in the Y-axes. Hence, the effective difference indynamic range preservation and voltage resolution between theconventional art and CVAT is well beyond 65,536/256. Hence, the currentHolter quantization has 0.39% of the resolution offered by CVATquantization rate. Additionally, during CVAT analysis a voltageoptimization (VO) bit interpolation process can be used to magnify theY-axes. Voltage optimization can be applied to selected regions of thevisually compressed file, individual heartbeats or selected waves withinit. Voltage optimization takes the selected part of the signal to 100%of it's potential above or below the isoelectric line. In the currentelectrocardiographic art, reliable detection of microvolt changes isconfined to costly and time consuming techniques such as signalaveraging done in the electrophysiologic laboratory and not useful formass screening or applicable to Holter analysis. Detection of certaintypes of microvolt changes is valuable as tool to identify serious riskfor arrhythmia. Such changes are usually more evident at times ofphysical and/or emotional stress. Ambulatory detection of microvoltchanges, applicable to mass screening is now made possible by CVAT andshould result in major improvement in cardiovascular diagnosis forprompt intervention and important reduction of mortality and morbidity.

[0199] Current Holter analysis relies upon signal amplitude (voltage)calibration done prior to recording by introduction of a 1 millivoltsignal directly into the magnetic tape. In theory this calibrationsignal should be equal in both channels and should render an even 10millimeters deflection when visualized in the electrocardiogram. If allgoes well, a 1 mm (0.1 mV) shift of the ST above or below theisoelectric line is to be taken as an electrocardiographic sign ofischemia. This concept is a direct extension of the very long experiencewith exercise tolerance testing done with stationary 12-leadelectrocardiographs, more precise instruments than the average Holterrecorder. In 12-lead electrocardiographs, the electronic gain can beadjusted at the time of calibration. In current Holter art, gainadjustment in the recorder is not possible. The Holter recordercalibration signal frequently has significant variation within andacross recorders and it does not give as reliable conversion factor formicrovolt evaluation as the 12-lead electrocardiographs.

[0200]FIG. 2 shows an example of uneven calibration signal in a Holterrecording. The size of the QRS voltage in the lower lead could be 4.4 or3.1 mm depending on which part of the calibration signal would be chosento represent 1 millivolt as a 10 millimeters deflection.

[0201]FIG. 3 shows the difference in the size of the calibration signalobtained from 3 different recordings, also note the difference in theheight of the signal in the lower channel of Holter C.

[0202] Reliance on the calibration signal to quantify the severity ofmicrovolt range changes around the isoelectric line is not as preciseand useful in Holter recording as it is in 12-lead electrocardiography.Conversion based on unreliable calibration hampers within and mostimportantly across patients comparisons. Furthermore, the voltage of theelectrocardiographic waves does not remain constant during the 24 hrHolter recording period. Voltage changes may be due to physiologic (e.g.positional, respiratory cycles, etc) as well as pathologic reasons(ventricular distention and mechanical incompetence of the ischemicventricle is an important reason for change). Under these conditions,absolute quantification of the ST segment, using the calibration signalas valid gage, may lead to erroneous conclusions. This is probably areason for the poor performance of current Holter analysis in detectionof myocardial ischemia.

[0203] More than 20 years ago, Marvin Ellestad M. D. called attention tothe importance of judging ST segment shifts as a percent of the QRS inthe same heartbeat. This work has been recently quoted in Ellestad M;American College of Cardiology Educational Highlights; Summer 1998:15-21 from which FIG. 4 was taken. This figure is used by Ellestad toemphasize the importance of describing ST segment deviation as a percentof the major deflection in the respective QRS. Ellestad observation isthe product of intensive and classic work in exercise stress testingdone with 12 lead electrocardiographs, better and more reliableinstruments than Holter recorders. Ellestad suggested 10% shift of theST as the cutoff point for the diagnosis of ischemia. However recentdata (“Association of Nonspecific Minor ST-T Abnormalities WithCardiovascular Mortality”, Daviglus M. L. et al. JAMA. 1999;281:530-536) indicates than even lower degrees of ST shift are likely tocarry increased risk of mortality and morbidity. In CVAT voltage changesare evaluated as percent of the dominant spike in the QRS deflection forwhich voltage is optimized to 100% of it's potential. Using CVAT,non-cardiology trained technicians can detect ST segment shifts as smallas 2% of the QRS.

[0204] The CVAT methodology for detection of myocardial ischemia usingST segment shift will now be described. Evaluation of the ST segment inisolation leaves most of the repolarization events out of diagnosticconsideration with consequent loss of valuable information. Most of theepicardial, and all the endocardial and mesocardial repolarization dataare not encoded in 60 to 100 milliseconds of the ST segment adjacent tothe J point. To be able to properly evaluate the T wave in the standard12 lead ECG, it is necessary to increase the paper recording speed from25 mm per second to 100 mm per second. The voltage gain must be doubledto inscribe 1 mV as a 20 mm deflection using a well maintained andcalibrated electrocardiograph. ECG recordings done in this manner haveenough detail to visualize all the repolarization nuances, especially, Twave morphology.

[0205] Current computerized Holter analyses compares only two 8-bitpoints. One 8-bit point in the ST segment (placed 60 to 100 ms beyondthe J point) is compared to an 8-bit point in the PQ segment which istaken to be the isoelectric line without regard or correction for thepresence of atrial ischemia (Ta). This is done with strict quantitativeadherence to the 1 mm shift (compared to the calibration signal) conceptderived from 12-lead electrocardiography. Current Holter analysisconsiders less than 1 mm shift as being normal, this results in a highrate of false negative Holter reports when algorithm analysis is notcompared to visual analysis of the analog signal by expertcardiologists. Current computerized Holter analysis does not domorphologic evaluation of the T wave. In current Holter analysis thedigital ECG file is not a complete and accurate representation of theoriginally encoded analog signal. To properly evaluate the ST segmentand the T wave it is imperative to have a high fidelity and resolutionsignal with optimum dynamic range. The ECG signal recovered by CVAT hasenough detail in the microvolt region to render precise details foraccurate evaluation of all the ECG. Current Holter algorithms lackdetail in the data stored and do not have the means to render a faithfuldepiction of the T waves recorded in the magnetic tape.

[0206] In Holter analysis, unreliable voltage calibration and unexpectedvoltage changes during the recording render the 1 mm shift at one pointin the ST segment a handy but imprecise extrapolation from 12 leadelectrocardiography. It will be a major improvement to evaluate the STsegment shift as what it is, a line, and not a single point as currentalgorithms do. The extent of the shift from the isoelectric line is bestdescribed as a percent of the largest voltage element of the QRS, asproposed by Ellestad more than 20 years ago. CVAT is able to do athorough evaluation of the ST segment and complement it with a completemorphologic evaluation of the T wave, a major index of myocardialrepolarization. CVAT can quickly identify shifts as small as 2% above orbelow the isoelectric line. Traditionally, minor changes in the STsegment and the T wave have been dismissed as “non specific” and withoutprognostic or diagnostic importance. However, recent data (“Associationof Nonspecific Minor ST-T Abnormalities With Cardiovascular Mortality”,Daviglus M. L. et al. JAMA. 1999; 281:530-536) link these “minor”abnormalities to increased mortality risk.

[0207]FIG. 5 shows the difference between the 1^(st) and 2^(nd)calibration signals in the lower lead as well as the marked voltagedifferences found within the recording period. Quantification of the STsegment shift will depend on which complex is taken as a gage; thechanging QRS voltage is another source of error. The morphology of the Twave is a valuable confirmation of abnormal repolarization which is notused by current computerized Holter analysis. The recording from whichthis figure was taken was not processed with voltage or dynamic rangeoptimization.

[0208]FIG. 6 show a minor example of the advantage of voltageoptimization in a recording digitized without optimizing dynamic range.In FIG. 6, a “minor” (less than 1 mm) ST segment depression in the lowerlead becomes evident and important after the signal is voltage optimizedin the lower lead. Current Holter analysis would consider this to be anon-diagnostic ST shift. The morphology of the inverted T wave, whichhas a fast inscribing initial limb that makes it symmetric andarrow-point-like (best seen in alternating beats), validates theischemic nature of the ST depression. The alternating morphologicdifference (arrow point like versus slightly rounded top) in the T wavesis suggestive of repolarization heterogeneity probably due to ischemia.Two consecutive voltage optimized T waves from the lower lead arefurther magnified in FIG. 7. In this figure, the ST shift is moreevident in the second beat and the morphologic differences inconsecutive T waves are obvious. Flutter waves are seen as the downwardsmall spikes going down from the isoelectric line. Detailed morphologicanalysis of a high fidelity enhanced quality signal is possible withCVAT and impossible with conventional Holter algorithms. With CVAT, muchgreater degrees of magnification than shown above are possible ifnecessary.

[0209] The visual compression and morphologic evaluation of theambulatory electrocardiogram will now be described. CVAT visual analogsignal compression is a powerful tool to expedite and add precision toHolter analysis. FIG. 8 is CVAT's visually compressed pattern of anormal ECG tracing showing the different components of the compressedsignal. This recording was done without optimizing the dynamic rangeprior to analog to digital conversion. Most of the lower lead has beenvoltage optimized and it shows the difference CVAT does when applied toa recording done without independent channel modulation of the dynamicrange. Normally, the P, PQ, J, ST, T and TP (PT band) are superimposedto each other to form a solid band in the middle of the visuallycompressed analog signal. The QRS band surrounds the PT band as alighter component where the individual heartbeats can be seen. Thedensity of the QRS band increases and decreases with increasing anddecreasing heart rates respectively. The QRS also shows the regularityor irregularity of the heart rate in characteristic patterns which allowquick recognition of a single heart beat blocked (dropped). Pathologysuch as intermittent conduction defects, sick sinus node (tachy-brady)syndrome atrial flutter, fibrillation, etc have distinctive patterns inthe QRS band. The best rate of visual compression depends on thesampling rate and heart rate. It ranges between 1/64 to 1/256. Thelowest rates of compression works best when the heart rate is fast orwhen the sampling rate is low and vice versa. Expansion of the patternin the window with resampling to higher rates or limitlessmagnification, whenever necessary, allow precise identification ofclassic electrocardiographic signs.

[0210]FIG. 9 is a composite of different recordings shown examples ofhow CVAT compressed analog displayed facilitate quick identification ofST segment shifts by technicians without biomedical training or skillsin electrocardiography. The upper lead shows compact patterns of STdepression. The PT band is seen with a solution of continuity in it'smiddle portion. The white area which hugs the isoelectric line iscomposed by the PQ and portions of the T (depending on the changes in Tmorphology) and TP. The lower band which moves into the negative voltagearea represents down shift of the J point, ST and portions of the T(depending of the morphology of the T wave). The black space separatingthe PT band into two diverging portions is patognomonic of ST shift. Inthe lower lead examples of ST elevation are collected. Notice that thearm of the bifurcated PT band which departs from the isoelectric linehas moved into the positive voltage area denoting ST segment elevation.A library of patterns can be used for training technicians who will doCVAT analysis. Expansion of this tracings show the classic signs ofischemia described in the PQ for atrial ischemia and the J point to theend of the T wave for ventricular ischemia. Transient conduction blocks,which can be secondary to ischemia, also have characteristic patterns.

[0211]FIG. 10 shows ST segment elevation and T wave changes in anexpanded view used to confirm the findings on the compressed pattern.FIGS. 11 and 12 show visually compressed patterns of episodes of STdepression with inversion of the T wave. FIG. 11 shows best the gradualonset and offset of the ST segment shift characteristic of a trueischemic episode. FIG. 13 shows an expanded view of ST depression withinverted T wave. FIG. 14 shows a short episode of ST depression with Tinversion. This episode most likely would not have been detected withconventional Holter analysis. If detected, it would have been dismissedsince it does not last one minute which is a convention for acceptanceof an episode in current Holter analysis. FIG. 13 also shows Ta as asign of probable atrial ischemia. This ECG sign is not commonly seenbecause of the lack of dynamic range, fidelity and resolution of currentECG tracings.

[0212]FIG. 15 shows non-consecutive segment (two beats each) from arecording done without independent gain modulation. In both leads, thefirst wave is the 1 mV calibration signal followed by pairs ofconsecutive beats taken from different parts of the recording. The firstbeat of each pair is as it was originally recorded (O) and the second(V) is voltage optimized using CVAT software. Both the upper and lowerleads are similarly treated. The 5^(th) pair in the lower lead, whichhas the lowest QRS voltage in the original signal, is the one whichshows the most distinct ST segment elevation in the voltage optimizedbeat in the lower lead and depression in the opposite lead. The STelevation can not be seen in the original beat. If we quantify the Swave in the original beat of the 5^(th) pair according to thecalibration signal, this S wave would be about 6 mm in total and the STelevation would not be equal to the 1-mm criterion. However the voltageoptimized, second beat of the 5^(th) pair, shows that the ST elevationis about 20% of the S wave. This figure shows well the constantvariation in the QRS voltage for which there is no adjustments possiblein the calibration-based ST shift quantitative approach.

[0213] In FIG. 16, the QRS band shows the regular irregularity of theheart rate due to atrial flutter in a patient who also has STdepression. Both are readily identified in the visually compressed CVATpattern.

[0214]FIG. 17 is an expanded tracing of the pattern showing atrialflutter and ST depression; the flutter waves are visible showing a 4:1ventricular capture rate. This degree of visualization of the ECG is notpossible with conventional Holter analysis.

[0215] Next, intermittent atrioventricular and intraventricularconduction defects are described. The conduction system is relativelymore resistant to ischemia than the rest of the myocardium; hence whenit is affected enough to show conduction blocks, a severe degree ofischemia must be suspected. Atrioventricular and intraventricular blockscan be readily found using CVAT. The nature of the conductionabnormality can be further defined by expanding and magnifying thesignal if necessary. In the compressed CVAT mode, conduction blocks havecharacteristic patterns.

[0216]FIG. 18 shows the compressed CVAT pattern of intermittent seconddegree AV block. The QRS band in the right size of the figure has gapswhich resemble a comb with broken teeth. FIG. 19 is an expanded view ofthis record in which the second-degree atrioventricular block is readilyvisualized. Two P waves are identified, the first does not conduct tothe ventricle, and the second triggers a ventricular contraction. Thepattern is repeated in consecutive cycles. Independent channel gain wasnot used in this recording.

[0217]FIGS. 20 and 21 show the visually compressed and expanded patternsof ventricular ischemia (ST elevation) and intraventricular conductiondelay. Atrial ischemia (Ta) is readily apparent in FIG. 21.

[0218]FIG. 22 shows alternating intermittent intraventricular conductiondefect (ICD) in the 1^(st) beat of the upper lead and the second beat ofthe lower lead. The beats are not contiguous, are placed next to eachother for comparison only. This patient had changes in the upper leadalternating with changes in the lower lead, suggesting a shiftinglocation of the ischemic area of the heart. Note the widened QRS, andthe initial slurring of the deflections in the 1^(st) upper and 2^(nd)lower beats. Compare these beats with their counterparts in the oppositeleads which have a near normal configuration. Note also that the T wavesfollowing the beats with abnormally conducted QRS have a differentconfiguration of the T waves compared with the other beats. The abnormalT waves reflect the disarray in repolarization consequent to theaberrant intraventricular conduction in the preceding QRS.

[0219] Current Holter algorithms lack integrity, dynamic range, fidelityand resolution and can not match human ability to recognize morphologicpatterns. For these and other reasons, current Holter analysis can notbenefit from the wealth of ECG signs of ischemia and it is limited todubious quantification of one point in the ST segment. CVAT is designedto identify all the valuable electrocardiographic signs described in thepeer-reviewed literature (mainly from studies done in exercise testinglaboratories) to improve Holter analysis and facilitate ischemiadetection.

[0220] T wave morphology changes as sign of abnormal repolarization willnow be described. Current Holter analysis algorithms rely onmathematical formulae which use calculated slopes and intersects in anattempt to identify electrocardiographic landmarks that are difficult toprecise even with visual magnification of specially taken 12 lead ECG's.Analog reconstruction of the T wave with current algorithms is poor dueto lost data, and poor fidelity, resolution and deterioration of thedynamic range of the scanty signal preserved. Morphologic evaluation ofincomplete electrocardiographic signal of poor quality is questionable,at best. The low quality of the highly compressed and filtered ECGsignal encoded by the current Holter algorithms does not permitretrieval of the analog electrocardiogram as it was encoded in themagnetic tape. CVAT recovers the intact signal and enhances it to createa rich digital file using state-of-the-art software dedicated topreservation of the dynamic range, high fidelity and resolution. CVATcan accurately magnify at will both the time and voltage domainsrendering ECG's of optimum quality suitable for all kinds ofmeasurements and morphologic evaluation.

[0221] The four beats in the upper and lower rows of FIG. 23 are thesame beats, duplicated from the same lead. This portion of the file hasbeen resampled from 44,100 Hz to 96,000 Hz in both rows. In the Y-axes,the voltage has been optimized in the lower row only. Note, in the lowerrow, the marching of the P wave into the T wave (second beat) to mergewith the T in the third beat. This kind of evaluation is not possiblewith current Holter algorithms.

[0222] Repolarization abnormality is a harbinger of potentially lethalarrhythmia (see “Electrical Alternace” below) myocardial infarction, orsudden death. Abnormal T wave morphology suggests myocardialintracellular changes which alter orderly, normal, cardiac cellrepolarization. Abnormal repolarization can be a consequence of abnormaldepolarization or ischemia and the cause of serious arrhythmia.

[0223] Under normal conditions, the T wave has the same polarity thanthe QRS deflection. Inscription of the T wave starts when the plateau ofthe action potential of the epicardium separates from that of the midmyocardial cells (mesocardium). As the voltage gradient between theepicardium and the mesocardium continues to expand, the ascending limbof the T waves is inscribed in the ECG at a slower rate than thedescending limb of the T wave. The ascending limb inscribes the peak ofthe T wave when the epicardium is fully repolarized. In the oppositeside of the ventricular wall, the plateau of the endocardial cell actionpotential separates from that of the mesocardial cell generating anopposing voltage gradient that limits the amplitude of the T wave andstarts inscription of the descending limb of the T wave. The fullrepolarization of the mesocardium marks the end of the T wave. The timeelapsed from the peak to the end of the T wave is an index of the degreeof transmural dispersion of repolarization. A disproportionateprolongation of the action potential in the mesocardium prolongs thetime from the peak to the end of the T wave (Tp-Te) and widens the T dueto slower rate of descent of the distal limb. This prolongation of theTp-Te may be also out of phase with changes in the R-R interval; i.e. itdoes not shorten or elongate proportionally when the heart rate increaseor decrease, respectively.

[0224] The internal harmony of repolarization intervals will now bedescribed. When electrocardiographic intervals are measured to assessrepolarization, the standard reference for comparison is correction toan “ideal” heart rate of 60 beats per minute. More important than thiscomparison is the lack of pari passu shortening of repolarization withshortening of the cycle length. The corrected QT (QTc) interval isconsidered a surrogate of the cellular action potential duration. The QTinterval includes electrical depolarization and repolarization of theventricles and is a limited reflection of the complex electrogenesis ofventricular repolarization. The QTc has been shown to be of no value topredict mortality or arrhythmic events (Circulation 1998; 97:2543-2550).A study (J Am Coll Cardiol 1987; 10:1313-21) in which 19 automated QTcmeasurement systems were compared found standard deviations as large as30 ms when locating the end of the T wave compared with 6 ms for the QRSonset. This study compared recordings done with conventional 12-leadelectrocardiographic equipment. The inferior quality of the Holterrecordings would give similar or greater standard deviations ifsubjected to the same type of study. Any evaluation of T wave durationis complicated by the T wave changing morphology within a recordingperiod. Valid diagnostic conclusions can not be based on impreciselandmarks, measurements “normalized” with formulae established for moreprecise and complete signal obtained with superior type of equipment andwhen the standard deviation of the method is probably larger than theelongation supposed to be clinically significant.

[0225] There are researchers who believe that T wave morphology is moreimportant than its total duration. The duration of repolarizationusually changes in unison and in harmony with the duration of eachheartbeat. Harmonic change is probably more important for diagnosis andprognosis than milliseconds of difference in “corrected” QT. The conceptof measuring the interval between the peak and the end of the T wave asa measure of ventricular repolarization has been proposed several yearsago (Antzelevitch et al J Am Col Cardiol; 1994; 23:259-77). This timeinterval represents the transmural dispersion of repolarization: thelonger it is the more fragmented and abnormal repolarization is likelyto be. Evaluation of the morphologic features of the ST segment and theT wave, looking for manifestation of electrical alternans, assessing theinternal coherence of the repolarization intervals and their concordantchange with heart rate variation are more valuable than the simpledetermination of the QTc.

[0226] The instant CVAT method proposes that better measurements ofrepolarization and its accommodation to changing heart rate are:

[0227] Duration of repolarization measured from the J point to the endof the T excluding the QRS since this complex reflects ventriculardepolarization.

[0228] Time from the J point to the end of the T (J-Te) reflectsepicardial, mesocardial and endocardial repolarization time

[0229] Tp-e stands for the time from the peak (Tp) to the end (Te) ofthe T wave as an expression of ventricular transmural repolarizationtime

[0230] Time from J point to J point (J-J) as a measure of one heart beatduration

[0231] (Tp-e/J-Te)×100 represent the relative duration of transmuralrepolarization time as a percent of the total duration of therepolarization. Prolongation of the transmural repolarization, indisproportion to the total duration of repolarization, is likely toreflect transmural repolarization dispersion, prolongation of thevulnerable period and heightened risk for ventricular arrhythmia. Thispercent value, determined continuously or at regular intervals (such asevery 15 to 60 minutes) plotted, in the Y-axes, against clock time ofHolter recording, in the X-axes, represent circadian variation in therelative duration of transmural repolarization.

[0232] (J-Te/J-J)×100 express the relative duration of totalrepolarization time (epicardial plus transmural) as part of total cyclelength and correlates total repolarization to heart rate. Normally, J-Teshould shorten as J-J shortens. Plotting this percent value versus clocktime will give an idea of the circadian variation in totalrepolarization time as part of it's own cycle length (and hence heartrate) from which valuable diagnostic and prognostic information could bederived.

[0233] Preliminary data suggests that normal repolarization (J-Te) maybe at or below 30% of the cycle length (J-J) and transmural (epicardialto endocardial) repolarization (Ta-Te) should also be at or below 30% ofJ-Te. Further work is being done by the instant inventor to furtherprecise these relationships.

[0234] In FIG. 24, the two consecutive beats in the upper row werecopied in the lower row. The ECG signal was resampled from 44,100 to96,000 Hz, in both leads. Only the lower lead was voltage optimized.This process can be used to expand the time and voltage domains forprecise identification of electrocardiographic landmarks. In thisfigure, the T wave has a symmetric (arrow point like) shape, differentfrom normal where there is a slower ascending than descending limb. TheJ-J is 791.5 ms (heart rate=76 beats per minute). J-Te is 237.5 ms, Tp-eis 50 ms. Hence, the transmural repolarization (Tp-e) is 21% of thetotal repolarization time (J-Te) and the total repolarization time(J-Te) is 30% of the total cycle length (J-J).

[0235] In FIG. 25, two consecutive beats are duplicated in the lowerrow, both were resampled, only the lower row was voltage optimized thecycle length is 1054.1666 ms (heart rate=56.9 beats per minute). Thefirst T wave J-Te is 279 ms; Tp-e is 96.6 ms or 34.6% of J-Te. Thesecond T wave J-Te is 291.6 ms; Tp-e is 83.3 ms or 28.5% of J-Te. Therelative longer duration of the transmural repolarization of the first Twave (Tp-e of 34.6% vs. 28.5% of their respective J-Te) coupled with thedistinctly different morphology and height (the first T is 2.5 timestaller and more peaked than the second) suggest heterogeneousrepolarization (electrical alternans).

[0236]FIG. 26 shows the opposite lead to that shown in FIG. 25, the twobeats opposite to those shown in FIG. 25 have been isolated. Significanthorizontal ST segment depression is shown. Electrical alternans andheterogeneous repolarization may be caused by myocardial ischemia.

[0237] In FIG. 27, ST segment depression and biphasic (+-configuration)T waves are present in both leads. The cycle length (J-J) is 783.3 ms(heart rate=76,5 beats per minute), J-Te is 458.33 ms, Tp-e is 195.83ms. Transmural repolarization (Tp-e) takes 42.7% of the totalrepolarization time (J-Te) which represents 58.5% of the cycle length(J-J). The relative prolongation of both the total and the transmuralrepolarization times is in keeping with the ST segment depression seenin both leads. Current Holter analysis would have placed the end of theT at an intersect with the isoelectric line based only on a line fitonto the down sloping arm of the first (positive) phase of the biphasicT. The negative phase of the biphasic T would have been excluded by theplacement of the slope. Furthermore, its unlikely that the degradedsignal would have shown the negative phase of the biphasic T. The STsegment depression has an upsloping trend; however, the ST fails toreturn promptly to the isoelectric line. The morphology of the ST inconjunction with that of the T wave strongly suggests ventricularrepolarization abnormality probably due to ischemia.

[0238]FIG. 28 is a tracing from the lower lead of the recording shownabove a little later in the recording period. Distinctly horizontal STsegment depression with T wave inversion is documented which confirm thelikelihood of myocardial ischemia in this patient.

[0239] The T waves in both leads of FIG. 29 are biphasic. In the lowerlead J-J is 912.5 ms (HR=65.7 bpm), J-Te is 458.3 ms (50.2% of J-J) andTp-Te is 270.1 ms; hence, 58% of the total repolarization is taken bytransmural repolarization. ST segment depression in the upper lead andelevation in the lower lead are also present.

[0240]FIG. 30 is a tracing taken later in the same recording as FIG. 29.Compared with the previous figure, note the more pronounced horizontalST depression in the upper lead and the ST elevation in the lower lead,confirmation of myocardial ischemia in this patient.

[0241]FIG. 31 shows three heartbeats in the same lead duplicated andresampled. Only the lower tracing was voltage optimized. The T wave hasdouble hump morphology. This tracing raises the question: Is thetransition from epicardial to endo-mesocardial repolarization at thepeak of the first hump?

[0242]FIG. 32 shows two heart beats (1st B and 2^(nd) B) located in thesame recording, same lead, 20 seconds apart. The 1^(st) and 2^(nd) QRSconstitute one cycle length and the 3^(rd) and 4^(th,) the second cyclelength.

[0243] The following measurements were taken from the first cycle lengthin FIG. 32: J-J 770.83 ms (77.8 beats per minute) J-Te 362.50 ms (47.0%of J-J) Tp-e 187.50 ms (51.7% of J-Te)

[0244] For the second cycle length: J-J 883.33 ms (67.9 beats perminute) J-Te 406.25 ms (45.9% of J-J) Tp-e 220.83 ms (54.3% of J-Te)

[0245] The positive phase of the biphasic T wave in the second beat is4.3 times (apex of the T to the isoelectric line) taller than the T wavewhich follows the first QRS. The double hump morphology shown in FIG. 31was observed in the same recording of the patient.

[0246] Work is ongoing by the instant inventor to further identifyadditional morphologic patterns, internal correlation of intervals andvoltages in normal subjects and patients with different cardiovascularpathology as well as during percutanoeus transluminal coronary arteryballoon dilatation.

[0247] The electrical alternans will now be described. Temporalheterogeneity in repolarization can be expressed in an individual beat(spatial heterogeneity seen as repolarization dispersion comparing thesame ST-T in two or more different leads) or in a sequence of beats(dynamic heterogeneity shown as differences in duration and/oramplitude) also known as electrical alternans. Electrical alternansrepresents heterogeneity of cardiac muscle repolarization and/ordepolarization as a consequence of myocardial ischemia and other formsof cardiac disease. It can be considered a harbinger of malignantarrhythmias.

[0248] Beat-to-beat microvolt alternation of the amplitude, unstablemorphology and/or changing polarity of the T wave are markers ofvulnerability to potentially lethal ventricular arrhythmia. There areresearch efforts to identify patients who have this electrocardiographicrisk marker using sensitive spectral signal-processing techniques inspecialized laboratories, by highly skilled electrophysiology experts.Electrical alternans documented during exercise induced tachycardia is abetter predictor of arrhythmia vulnerability than signal averagedelectrocardiography (Estes N A et al. Am J Cardiol 1997; 15:1314-8) orelectrophysiologic testing in the cardiac catheterization laboratory(Hohnloser S H et al J. Cardiovasc Electrophysiol 1996; 7:1095-111).

[0249]FIG. 33 is a 16 seconds consecutive strip from a recordinganalyzed with CVAT. Macroscopic beat-to-beat variation of the T wavemorphology is noticeable; especially the peculiar morphology of the Twave that precedes the premature beat (PB). CVAT allows visualidentification of beat-to-beat T wave morphologic changes whichcorrespond to microvolt beat-to-beat variations in repolarization.Current Holter analysis lacks signal quality and quantity to match CVATaccurate morphologic analysis. CVAT brings into daily clinical practicea diagnostic tool heretofore available only as a costly experimentaltool in few research laboratories and not yet applicable to patient careor large scale risk screening, both possible with CVAT.

[0250] Measuring time intervals in the Holter electrocardiogram is nowdiscussed. As it is the case with data on microvolt range ECG signals,knowledge on electrocardiographic time intervals is the result ofstudies and experienced acquired using well maintained, standardized andcalibrated stationary 12-lead electrocardiographs. Concepts arrived atin this manner were extended to Holter analysis. However, the followingare some of the reasons to believe that the 12-lead ECG intervals arenot necessarily applicable to the evaluation of ambulatoryelectrocardiography:

[0251] Holter recordings are done with relatively simple, battery-drivenmotors which run at very slow speeds without feedback regulation of thespeed drive. The magnetic tape runs across the recording head atcritically low speeds of 1.1 to 0.55 mm per second. Ten percentfluctuations in speed are said to be common in Holter recordings, andprobably a 3% variation is the best that can be expected with the bestequipment available today which is not used outside of few researchcenters. This factor of error in the conversion from time in therecording to real (24 hr) time is usually not accounted for. Servocontrol and closed loop technology can improve the steadiness of thetape transport speed at the critically low speeds needed but have notyet been incorporated into commercial Holter recording. The instantinventor is researching better technology and media to be used for theambulatory recording of biologic waves.

[0252] Very fast play back of Holter recordings done at critically lowspeeds are another factor for the potential distortion of the timeintervals and variation both within and across equipment used.

[0253] Tape stretch, wow, flutter, tape biasing etc. are likely tointroduce more problems leading to less than precise determination ofthe duration of the intervals in the ambulatory electrocardiogram.

[0254] In current Holter analysis, duration of the QT and otherintervals is measured in milliseconds. CVAT technology can measure downto one 10,000^(th) of a millisecond of real time in recordings digitizedat 44,100 or 96,000 Hertz per second. Recordings digitized at 44,100 Hzcan be resampled at 96,000 Hz. Sampling rates higher than 96,000 Hz arebeing tested. Lacking steady recording speed during Holter recording,absolute time measurements have to be interpreted with caution as usefulto judge relative duration of different elements within a recording, butdifficult to extrapolate and compare across recordings or acrosspatients. Hence, in CVAT, internal concordance, as an expression ofharmonic relationships within the electrocardiographic intervals of agiven patient, is considered more important than absolute timemeasurements. It is believed that judging intervals relationship as anexpression of harmonic continuity of electrophysiologic cardiac functionis more useful than “correcting” time intervals using formulas developedfor 12-lead electrocardiography. Basset's QTc and other formulas correctthe QT interval using as reference “normal” population intervals at anideal heart rate of 60 beats per minute. The formulas were derived fromand for 12-lead electrocardiography. Critically low recording speeds,variable play back rate, tape stretch, wow flutter etc do not exists asfactors of error in 12-lead ECG interval measurement. Hence, correctionfactors developed for 12-lead ECG are probably unsuitable forapplication to conventional Holter analysis.

[0255] Until better Holter recording equipment (e.g. with servocontrolled recording speed and with precise 10,100 and 500 Hzcalibration) will be commonly available, the advantages of the CVAT modeof analysis can be applied to Holter recordings done with currentlyavailable equipment.

[0256] The 1 millivolt per second signal used today can be a used as agage to measure time intervals. Across patient and across recorderscomparisons may not be as precise as CVAT can be, but search for withina recording harmony of time intervals can be done until better recordingequipment will be available.

[0257] Using Sound Forge, a window is opened to record 5 to 10 secondsof silence (a blank canvas) at identical sampling rate than that used tostore the analog signal into the hard drive. The input format usedshould be samples per second. A 12 to 15 cycle length calibrationsignals is copied into the canvas from the middle or most stable part ofthe calibration period in the recording to be analyzed. Any beats, orwaves within a beat, which need to be measured are also copied from therecording being analyzed into the canvas.

[0258] The first step is to expunge the areas of each beat which do notrequire precise duration measurement. Unless there is a need to measureQRS duration it is best to eliminate the QRS from the canvas. If notexpunged, the height of the QRS becomes an obstacle for maximummagnification of the P and T waves using the voltage optimizationfeature of CVAT. Magnification of the P and T waves using pixelinterpolation is a great aid for precise identification of the beginningand end of the waves. Resampling to a higher sampling rate expands thetime domain and adds precision to time intervals measurement. Using CVATtime intervals can be measured to the 10,000 th of a millisecond.

[0259]FIG. 34 shows a canvas in which the signal in the upper channelwas copied into the lower channel for the purpose of demonstration ofthe steps described above. Both channels were resampled from 44,100 to96,000 Hz. Only the lower channel was voltage optimized. The recordcalibration voltage waxed and waned in height between 68 and 100%. Thisis a reason not to trust voltage measurements from Holter recordings.Six calibration cycle lengths on either side of the tallest signal in aperiod located about the middle of the calibration segment weretransported into the canvas. In FIG. 34, 10 calibration cycle lengthswere isolated; cursors were placed at the apex of the first and lastsignal with the recording opened at 1:1 scale for best visualization andprecise placement of the markers. The 10 cycle lengths measured as23,274 samples; hence

[0260] One cycle length=1second=2,327.4 samples.

[0261] This is the constant used to calculate the time periods in thisrecording and in the FIGS. 35 to 38.

[0262]FIG. 35 shows one heartbeat with the cursors placed at the apex oftwo consecutive R waves with the screen opened at 1:1 ratio, to fit thefigure into a size suitable for reproduction, the window was contractedto 1:2 ratio. There were 2,153 samples from R to R, hence2,153/2,327.4=0.9250665 seconds which gives an instantaneous heart rateof 64.86 beats per minute.

[0263] To obtain the full benefit of voltage optimization of the P and Twaves, the central portion of the QRS was excised in FIG. 36. Aftervoltage optimization the tracings were further magnified to bestvisualize the microvolt components of the ECG and allow preciseidentification of the T and P morphology. The small sharp spikes betweenthe P and the T waves are the take off of the R wave and the return tothe isoelectric line of the S wave. These landmarks have been left toidentify the PR and J points respectively, as noted in the figure.

[0264]FIG. 37 is a close-up of the beat used to calculate theinstantaneous heart rate in FIG. 34. Cursors were placed at the J pointand at the end of the T wave (Te) located visually with the windowopened at 1:1 scale. Precise placement of the cursor at the end of the Twas verified as the intersect of end of the negative phase of thebiphasic T with a line traced from the beginning of two consecutive Pwaves taken as the isoelectric line. The number of samples from the Jpoint to the end of the T wave were 1,163 which divided by the number ofsamples for one second (2,327.4) equals 0.4996992 seconds.

[0265]FIG. 38 shows time measurement from the apex of the T (Tp) to theend of the T (Te) for the same beat in a 1:1 scale. Tp-Te equals692samples divided by the constant 2,327 equals 0.2973274 seconds formesocardial and endocardial repolarization time. FIG. 38 also shows thedifference (black area) that would exist between an automated slopebased T wave measurement and CVAT. The algorithms for automated QTinterval measurement from Holter tapes would fit a slope on thedescending limb of the positive (first half) segment of the biphasic Twave. By doing so the algorithms would disregarded the 450 samples ofthe negative phase of this biphasic T. A slope based measurement wouldhave resulted in 450 samples, or 0.1933488 seconds, shorter T wave (J-Teat 0.3063504 seconds instead of 0.4996992 seconds), a greater differencethan that between normal and pathologic states JT dispersion andcircadian variation and relationship with R-R (J-J) changes can bemeasured by selecting 5 to 10 beats at regular intervals depending onthe purpose of the measurement. Within the constrains imposed byvariation in the tape recording speed, CVAT gives a better measurementof time intervals than current algorithms.

[0266] Next, the evaluation of implanted pacemakers function inaccordance with CVAT will be described. The high fidelity, high dynamicrange of CVAT makes it suitable for pacemaker function evaluation.

[0267]FIG. 39 shows an excerpt of one lead of a recording showingcalibration signals and paced beats. The average duration of one cyclelength of the calibration signals is 992.5 samples, which is to be takenas being equal to one second in this recording. The time between thefirst and second pacemaker spike is 979 samples divided by 992.5 equals0.9863979 seconds. There are 14 samples from the beginning of thepacemaker spike in the 1st beat to the apparent take off of theventricular depolarization which equals 0.0141057 seconds. The 4thventricular depolarization is not pacemaker triggered and happens at0.6811083 seconds (676 samples) from the previous pacemaker spike. The5^(th) ventricular depolarization is pacemaker triggered at 1.0448362seconds from the onset of the non-pacemaker triggered ventriculardepolarization. It seems that the 5^(th) pacemaker spike happened whenspontaneous ventricular depolarization had just started similarly to the8^(th) depolarization which started 1.0508816 seconds after the onset ofthe spontaneous 7^(th) depolarization in this series of consecutivepaced and non paced beats. FIG. 40 is a close up of these paced beats.To the best of the inventors' knowledge, this kind of evaluation is notpossible with current Holter algorithms.

[0268] CVAT's application to on-line electrocardiographic monitoring inintensive care areas will now be described. It is known that traditionalon-line electrocardiographic monitoring is efficacious for arrhythmiadetection done with QRS driven algorithms. However, on line detection ofischemia is unreliable and alternative methods, such asvectocardiography, are being intensively tested. Vectocardiographyrequires very skilled operators and it is not cost effective forwidespread use. CVAT compressed patterns facilitates ischemia detectionby those unskilled in electrocardiography, including patients, after avery brief instruction period.

[0269] For on-line use of CVAT, the ECG signal is split and fed to anoscilloscope and to the sound card of a computer (including palm and laptops). The signal is displayed in one CRT or LCD screen with twowindows. One window shows the real time ECG, another shows the 1/64 to1/256 (according to the heart rate) visually compressed CVAT signalcorresponding to the last 2 or more minutes. The CVAT visuallycompressed analog ECG clearly shows ischemic patterns which in the realtime display are likely to go unnoticed because of their slow onset,observers lack of electrocardiographic sophistication, visual fatigueetc.

[0270] CVAT's application to sleep apnea will now be described. A smallmicrophone is used to record respiratory sounds preferably from the areasurrounding the upper airway between the soft palate and the larynx. Thesound signal is fed into one channel of a Holter recorder which is usedto simultaneously monitor two ECG leads (one right and one leftprecordial lead). Sound frequency analysis is used to recognize normalbreathing sound from snoring and apneic spell induced by central orperipheral sleep apnea. The simultaneously recorded electrocardiogram isused to monitor the impact of sleep apnea in cardiac electrophysiology,and determine the need for appropriate therapy. This apparatus andmethod can replace costly in-hospital somnographic studies and provide acost-effective mean to diagnose and monitor sleep apnea patients athome.

[0271] Experimental Results

[0272] A Comparison of the Results of Paired Analysis of Holter TapesUsing a Conventional Algorithm and CVAT

[0273] Objective

[0274] The purpose of this study was to compare the relative efficacy oftwo different computer-aided 24 hours Holter monitoring analysistechniques to detect ischemia in 24 hours magnetic tape Holterrecordings.

[0275] An officer of the company which provided the Holter tapes and acopy of the corresponding report, selected the tapes to be analyzed.Initially, at the request of the CVAT inventors and analyzer, tapesknown to have signs of ischemia were selected. Later in the study,random tapes were sent for CVAT analysis. Hence, a selection bias wasinitially introduced, at the request of the CVAT analyzer; suchconscious bias should work against CVAT and in favor of the algorithmmethod.

[0276] A total of 67 tapes were analyzed by both methods and thefindings are reported below. The Holter recorded analog signal, asretrieved by the CVAT technology, is archived in compact discs to avoidtape stretch and other artifacts, should reanalysis be desired. Thereports are identified by the five-digit number assigned at the sourceof the Holter tapes followed by a capital letter-which identifies thecompact disc in which the analog signal is kept.

[0277] A state-of-the-art computer algorithm was compared to the instantCVAT method for the retrieval, uploading and analysis of the ECG signalencoded in the Holter magnetic tapes. All the electrocardiographic signsdetected with CVAT are classical for ischemia as described in standardelectrocardiography textbooks and peer reviewed journals.

[0278] Results

[0279] The following table identifies the tapes which had:

[0280] No ischemia

[0281] Ischemia found by both the algorithm and CVAT

[0282] Ischemia detected by the algorithm but not by CVAT and

[0283] Ischemia identified by CVAT but not by the algorithm ISCHEMIAISCHEMIA FOUND BY FOUND BY ISCHEMIA CVAT AND ALGORITHM FOUND BY NOISCHEMIA ALGORITHM ONLY CVAT ONLY N = 5 N = 12 N = 1 N = 49 87247 A87250 A 87251 A 87138 A 87240 B 87246 B 87245 B 87133 B 87083 C 87015 C87016C 86952C 87084 D 87115 D 87132 D 87143 0 87253 E 87321 E 87344 E87331 F 87337 F 87339 F 87341 F 87325 G 87327 G 87340 G 87442 G 87438 H87441 H 87443 H 87450 H ISCHEMIA ISCHEMIA FOUND BY FOUND BY ISCHEMIACVAT AND ALGORITHM FOUND BY NO ISCHEMIA ALGORITHM ONLY CVAT ONLY 87356 J87369 J 87371 J 87372 J 87376 K 87377 K 87378 K 87379 K 87380 L 87383 L87385 L 87479 L 87490 M 87495 M 87497 M 87499 M 87480 N 87494 N 87498 N87496 N 87500 O 87507 O 87513 O 87536 O 87510 P 87523 P 87525 P 87526 P87527 Q 87528 Q 87529 Q 87533 Q 87535 R 87537 R 87538 R 87544 R

[0284] Hence 62 of the 67 tapes analyzed had ischemicelectrocardiographic signs. Of these 62, one (1.5%) was detected by thealgorithm only, 12 (20%) by both the algorithm and CVAT, 61 (98.4%) byCVAT and 49 (78.5%) by CVAT only.

[0285] The following results deserve comment:

[0286] Holter No 87084 D

[0287] Was the only tape in which the algorithm foundelectrocardiographic signs of ischemia and CVAT did not. This is asingle lead recording of less than optimum quality, the algorithm foundST elevation in this single lead. CVAT did not find ST elevation but Jdepression with biphasic and inverted T waves. To keep the bias constantand against CVAT, this will not be considered a false positive finding.

[0288] Holter Tapes in Which Ischemia was Found by Both, the Algorithmand CVAT

[0289] 87250 A

[0290] The algorithm found ST depression in the upper lead only CVATfound ST depression in both leads

[0291] 87251 A

[0292] The algorithm found ST depression in the upper lead only CVATfound ST depression in both leads

[0293] 87240 B

[0294] The algorithm found ST segment “sagging” in the upper lead onlyCVAT found ST depression in the upper lead and elevation in the lowerlead

[0295] 87083 C

[0296] The algorithm found slight ST depression in the upper lead CVATfound ST depression in the upper lead and elevation in the lower lead

[0297] 87016C

[0298] The algorithm found ST depression in the upper lead CVAT found STdepression in the upper lead and elevation in the lower lead

[0299] 86952 C

[0300] The algorithm found ST depression in the upper lead CVAT found STdepression in the upper lead and elevation in the lower lead

[0301] 87441 H

[0302] The algorithm found ST depression in the upper lead only CVATfound ST depression in the upper and lower lead with shifts to STelevation in the lower lead

[0303] 87356 J

[0304] The algorithm found ST depression in the upper lead only CVATfound ST depression in the upper and lower leads

[0305] 87372 J

[0306] The algorithm found ST depression in the upper lead CVAT found STdepression in the upper lead and elevation in the lower lead

[0307] 87526 P

[0308] The algorithm found 2 minutes of ST depression in the upper leadCVAT found constant ST depression in the upper lead with ST depressionshifting to elevation in the lower lead.

[0309] The algorithm and CVAT had concordant ST segment findings intapes No 87138 A and 87253 E only. In both instances, the ST segmentdepression was in the upper lead only. In 10 out of 12 tapes thealgorithm did not find ST shifts in the lower lead which were detectedby CVAT. The right precordial lead seems to be the one recorded in thelower lead and frequently it is of lower voltage (and hence dynamicrange) than the upper lead. The lower voltage probably renders the rightprecordial lead more susceptible to greater obliteration of the signalby the under-sampling, compression, smoothing and filtering used by thealgorithm.

[0310] Conclusion

[0311] Of the 62 patients who had ischemic electrocardiographic signs inthe Holter tapes., 61 (98.4%) were detected by CVAT and 13 (20.9%including a probably false positive finding) by the algorithm. Thisratio is similar to previous experience comparing algorithms versusvisual analysis of the magnetic tape where eight or nine out of tenpatients known to have ischemia were missed by different algorithmstested. In 10 of 12 instances of ischemia detected by both methods, thealgorithm failed to detect ischemic signs in the right precordial lead.The high rate of ischemia found in the total sample is notrepresentative of the general population but probably reflectspre-selection bias introduced by the perceived need for Holterevaluation as part of a cardiovascular work up. It is known that acommon reason for arrhythmia is myocardial ischemia, be it symptomaticor silent.

[0312] As explained in detail above, the instant invention usesalgorithms and software in a novel way for the analysis of electric,magnetic and/or pressure waves of biological origin with the purpose offacilitating the diagnosis of pathologic states in human and veterinarymedicine. The technique is applicable (but not limited to) the analysisof signals encoded in the electrocardiogram, electroencephalogram,myography, nerve conduction, plethysmography and other respiratoryfunctions, blood, intracardiac, intracerebral and other vital fluidpressures.

[0313] As explained above, an actual reduction to practice has been doneusing the algorithm encoded in the SOUND FORGE XP, VERSION 4.0 software,developed and marketed by SONIC FOUNDRY, a company located at 754Williamson St. Madison, Wis. 53703. Another program used is the EASY CDCREATOR, DELUXE EDITION, developed and marketed by Adaptac, Inc. 691South Milpitas Blvd., Milpitas Calif. 95035. The signal processed totest the instant invention was obtained through Holter recordings of theambulatory electrocardiogram.

[0314] In accordance with the invention, the analog signal from, forexample, a Holter recording, is digitized, not to subject the digitalfile to analyzes through mathematical, algebraic, neural network or anyother type of algorithms, but to optimize the high fidelityreproduction, reconstruction, compaction, etc. of the signal tofacilitate quick visual scanning of the dynamic electrocardiogram.Improving the state of the art sensitivity and specificity of theanalysis while preserving cost effectiveness are primary objects of thepresent invention.

[0315] The digital file is used to reconstruct a high fidelity renditionof the originally recorded analog signal for visual analysis usingdifferent rates of compression (compaction) of the original wave form tofacilitate visual searching for the classic electrocardiogram signs ofischemia which have been described heretofore mainly during studies ofischemia induced during exercise tolerance testing and lately duringpercutaneous balloon dilation of the coronary arteries.

[0316] In accordance with a preferred embodiment of the instantinvention, the signal is digitized at 44,1000 HZ/SEC versus 125(commercial) and 500 HZ/SEC (Harvard) using 16 bits instead of theconventional 12 bits. This feature enables at least one or more ordersof magnitude improvement in the measurement of wave amplitude andduration. Off the shelf sound editing software is preferably used tooptimize the digital storage of the analog signal to then do digitallyenhanced, high fidelity reconstruction of the analog signal. Thedigitized wave files are also suitable for compression to facilitatetheir transport through different media. The instant invention enablesreconstruction and optimization of poor signals originally recorded intothe magnetic tape.

[0317] The invention enables quick scanning and identification ofelectrocardiographic abnormalities by using the following techniques:

[0318] digital acquisition of the ECG analog signal from the Holter tapeat 44,100 (or higher) HZ/SEC;

[0319] digitize through 16 bits card or higher;

[0320] reproduction and optimization of the analog ECG signal using ahigh fidelity music editing software program such as SOUND FORGE;

[0321] Visual analysis of the reconstructed compacted analog ECG signalis facilitated by the use of different rates of compression anddecompression as well as the proper colors to enhance the contrastbetween the signal and the background. The particular heart rategenerally determines the optimal rate of compression which preferablyranges between 1/32 and 1/256. Color further facilitates an accuratevisual analysis thereof. It has been found that the use of a red signalon a black background provides the best contrast, but other colors, aswell as black and white, may be used;

[0322] normalization, signal smoothing, image contrast enhancement, andgain increase available for example, in music editing program such asSOUND FORGE, are also tools which can optionally be used during analogsignal preparation and reconstruction;

[0323] The invention has identified a number of compacted analog signalpatterns some of which are shown and described herein, which point todiscrete classic electrocardiographic abnormalities including, but notlimited to, all the classic signs of myocardial ischemia describedheretofore. All forms of electrical alternans are readily identifiedusing these patterns. Familiarity with these patterns is crucial for thequick identification (at a fast scanning rate) of abnormal states whichcan be done by individuals, such as high school graduates with minimumtraining; and

[0324] electrocardiographic analysis is thus reduced to a patternrecognition process accessible to all health care personnel and notrestricted to highly skilled, cardiology trained professionals;

[0325] In accordance with the instant invention, suitable hardware andsoftware can be used for direct digital acquisition of the signal (toreplace initial storage into magnetic tape) through long periods (days).

[0326] It is noted that the inventor has determined that red signals andblack backgrounds provide the best contrast for viewing most of thesignals in accordance with the instant invention. The instant inventorhas found that visual analysis is easier when such a color contrast isused. In fact, it has been determined that in many instances black andred contrast provides optimal conditions for the visual analysis.

[0327] It is also noted that the graphs herein are only exemplary andthat other patterns may be used in accordance with the instantinvention. The instant invention enables 24 hrs of recorded heartbeatsto be accurately analyzed visually in approximately 20 minutes or less,thereby making visual analysis cost effective while also improving thedetection of abnormalities.

[0328] While the preferred forms and embodiments of the instantinvention have been illustrated and described it will be apparent tothose of ordinary skill in the art that various changes andmodifications may be made without deviating from the inventive conceptsand true spirit of the invention as set forth above, and it is intendedby the appended claims to cover all such changes and modification whichcome within the true scope of the invention.

What is claimed is
 1. Method of analyzing biological signals, comprisingobtaining a magnetic recording media having an analog biological signalrecorded thereon, using digital processing software to digitize saidbiological signal, displaying said processed biological signal in analogform on a display, and visually analyzing said biological signal on saiddisplay.
 2. Method of claim 1, wherein said biological signal is anelectrocardiogram.
 3. Method of claim 1, further including performingindependent channel enhancement of the dynamic range of said analogbiological signal prior to said digitizing.
 4. Method of claim 1,wherein displaying includes displaying said biological signal in timecompressed form.
 5. Method of claim 1, wherein visually analyzingincludes attempting to match patterns in said biological signal with agiven library of patterns.
 6. Method of claim 1, wherein electronicindependent optimization of the dynamic range in each channel is doneprior to said digitizing.
 7. Method of claim 1, wherein said digitizingis performed by sampling said biological signal at at leastapproximately 44,100 Hz per second per channel.
 8. Method of claim 7,wherein said digitizing is performed using quantization of at least16-bits per sample per channel.
 9. Method of claim 1, wherein saiddigital processing software is digital audio processing software. 10.Method of claim 1, further including the step of using time intervals inthe biological signal to asses internal functional harmony of thebiological signal.
 11. Method of claim 1, wherein digitizing includesusing computer sound cards to digitize the biological signal.
 12. Methodof claim 1, wherein visually analyzing said displayed signal includeslooking for abnormalities from the group consisting of: myocardialischemia, arrhythmia, repolarization, depolarization heterogeneity, andpacemaker malfunction.
 13. Method of claim 1, wherein said displayingincludes magnifying said displayed biological signal in a Y axis toenable at least microsecond levels of said biological signal to beviewed.
 14. Method of claim 1, wherein said displaying includesmagnifying said displayed biological signal in an X axis to enable atleast microvolt levels of said biological signal to be viewed. 15.Method of claim 1, further including using said method for massscreening of the human population for abnormalities.
 16. Method of claim1, wherein said magnetic recording media is a cassette tape and saiddigitization includes using a slow playback speed for said cassettetape.
 17. Method of claim 16, wherein said slow playback speed isselected to be approximately 40 mm per second.
 18. Method of claim 8,wherein said magnetic recording media is a cassette tape and saiddigitization includes using a slow playback speed for said cassettetape.
 19. Method of claim 1, wherein said biological signal is anelectroencephalogram.
 20. Method of claim 1, wherein said biologicalsignal is a myogram.
 21. Method of claim 1, wherein said biologicalsignal is a phonocardiogram.